FMK_DataSheet_MedChemExpress
LY294002_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:LY294002 is a broad–spectrum inhibitor of PI3K , with IC 50 of 0.5/0.57/0.97 μM for PI3Kα/δ/β, respectively, also potently inhibits CK2with IC 50 of 98 nM.IC50 & Target: IC50: 0.5/0.57/0.97 μM (PI3Kα/δ/β)[1]IC50: 98 nM (CK2)[2]In Vitro: LY294002 (5 μM) completely inhibits the phosphorylation of PKB In HepG2 cells. LY294002 (5 μM) is also shown to block insulin–induced phosphorylation of PKB Ser 473 in CHO–IR cells [1]. LY294002 is also a potent inhibitor of CK2 (casein kinase 2) with IC 50of 98 nM. LY294002 is also able to reduce the kinase activity of both isoforms of the serine/threonine kinases GSK3α and β[2]. When the CNE–2Z cell line is cultured in medium containing LY294002(0 μM, 10 μM, 25 μM, 50 μM, and 75 μM) for 24 h and 48 h, cell proliferation is remarkably decreased in a dose–dependent fashion [3].In Vivo: Treatment with LY294002 (i.p.,50 mg/kg, 75 mg/kg) significantly reduces mean NPC tumor burden as compared with the control group. Treatment with 10 mg/kg or 25 mg/kg LY294002 is less effective in decreasing tumor burden. Mean NPC tumor burden treated with LY294002 is remarkably decreased in a dose–dependent manner, whereas mean body weight is no obvious difference between control and treated groups (LY294002, 10 mg/kg, 25 mg/kg, 50 mg/kg, and 75 mg/kg)[3].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[2]PI3K inhibition by PI828 and LY294002 is determined in a radiometric assay using purified, recombinant enzymes (class IA and class IB) with 1 μM ATP. The kinase reaction is carried out for 1 h at room temperature (24°C) and is terminated by addition of PBS. IC 50 values are subsequently determined using a sigmoidal dose–response curve fit (variable slope). CK2 andGSK3β (glycogen synthase kinase 3β) inhibition is established by kinase selectivity screening. Inhibitor (10 μM; PI828 and LY294002)is tested against the Upstate panel of kinases in 10 μM ATP [2].Cell Assay: LY294002 is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.5%) before use [3].[3]Human nasopharyngeal carcinoma cell line CNE–2Z is seeded into 96–well plates at 5000 cells/well. Twenty–four hours after cells are seeded, the medium is removed and replaced in the presence of LY294002 (0 μM, 10 μM, 25 μM, 50 μM, and 75 μM) dissolved in DMSO or DMSO only for an additional 24 h and 48 h. To avoid any nonspecific toxic effects of DMSO on cell growth, DMSO concentrations are maintained at 0.5% in all experiments. MTT dye (5 mg/mL) is added to each well. The reaction is stopped by the addition of DMSO, and optical density is measured at 490 nm on a multiwell plate reader. Background absorbance of the medium in the absence of cells is subtracted. All samples are assayed in triplicate, and the mean for each experiment is calculated. Results are expressed as a percentage of control, which is considered to be 100%[3].Animal Administration: LY294002 is dissolved in vehicle (DMSO). [3][4]Mice [3]Athymic nude mice are used when they are 6–8 weeks. Mice are randomly divided into free separated into five groups (n=4 mice).Product Name:LY294002Cat. No.:HY-10108CAS No.:154447-36-6Molecular Formula:C 19H 17NO 3Molecular Weight:307.34Target:PI3K; Casein Kinase; Casein Kinase; Autophagy Pathway:PI3K/Akt/mTOR; Stem Cell/Wnt; Cell Cycle/DNA Damage;Autophagy Solubility:DMSO: 14.9 mg/mLMice are housed in the same environment with controlled temperature, humidity, and a 12 h light/dark cycle. Mice are inoculated subcutaneously with CNE–2Z cells (1×106 cells/mouse in 200 μL of RPMI–1640) into the flank. The tumor take rate is 100%. After 1 week, an intraperitoneal injection is performed to the xenograft mice with different dosage of LY294002 (10 mg/kg, 25 mg/kg, 50 mg/kg, and 75 mg/kg twice weekly (n=4 mice), each group for 4 weeks. Treated mice are monitored any signs. Body weight and tumors size are measured twice a week. Tumor size is measured using calipers and tumor volume is calculated (volume=longaxis×short axis2). At the end of the treatment, all mice are euthanized. One part of tumor tissue is fixed in formalin and embedded in paraffin, and another part is stored at –70°C.Rat[4]Male Sprague–Dawley rats weighing 220–240 g are anesthetized by intraperitoneally injecting pentobarbital sodium (50 mg/kg). The animals are divided into 3 groups: NMDA+vehicle (DMSO) (n=46), NMDA+LY294002 (50 nmol) (n=25), and NMDA+Wortmannin (50 nmol) (n=23). Either LY294002 or wortmannin mixed with 200 nmol of NMDA in a total volume of 5 μL is injected into the vitreous cavity of one eye. The same volume of DMSO is injected into the vitreous cavity of the contralateral eye, which is used as a control. The injections are performed under a microscope using a 32–gauge needle, which is connected to a microsyringe. The needle is inserted approximately 1 mm behind the corneal limbus. Damage to neurons and blood vessels in the retina is assessed at 2 and 7 days after the injection. The effects of the intravitreal treatment with either LY294002 or Wortmannin alone on retinal neurons and blood vessels are also examined.References:[1]. Chaussade C, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007 Jun 15;404(3):449–58.[2]. Gharbi SI, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15–21.[3]. Jiang H, et al. Phosphatidylinositol 3–kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma invitro and in vivo. J Exp Clin Cancer Res. 2010 Apr 22;29:34.[4]. Ueda K, et al. Differential effects of LY294002 and wortmannin on neurons and vascular endothelial cells in the rat retina. Pharmacol Rep. 2013;65(4):854–62.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
MedChemExpress抑制剂Cocktail家族全系列产品,为您的蛋白质检测保驾护航!
MCE抑制剂Cocktail家族全系列产品，为您的蛋白质检测保驾护航！“曾经，有一批待检蛋白摆在我的面前，我没有及时检测，等到它降解了，我才后悔莫及。
实验中最痛苦的事莫过于此……只能，再提一批！”实验室的故事，说多了都是泪啊。
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还好有MCE inhibitor cocktail家族为您的蛋白质提供全方位的保护。
蛋白酶抑制剂、磷酸酶抑制剂、去乙酰化酶抑制剂……不管您的课题是细胞通路、肿瘤研究、蛋白组学研究、免疫研究等，总有一款适合您！快点击以下产品链接，申请免费试用吧！MCE抑制剂产品介绍HY-K0010Protease Inhibitor Cocktail (EDTA-Free, 100X in DMSO)用于细胞裂解与组织抽提。
HY-K0011Protease Inhibitor Cocktail, mini-Tablet (EDTA-Free)用于细胞裂解与组织抽提，片剂更便于使用。
HY-K0021Phosphatase Inhibitor Cocktail I (100X in DMSO)有效抑制碱性、丝氨酸/苏氨酸磷酸酶。
HY-K0022Phosphatase Inhibitor Cocktail II (100X in ddH2O)有效抑制酸性、碱性、酪氨酸磷酸酶。
HY-K0023Phosphatase Inhibitor Cocktail III (100X in DMSO)有效抑制碱性、丝氨酸/苏氨酸磷酸酶。
HY-K0030Deacetylase Inhibitor Cocktail (100X in 70% DMSO)有效抑制蛋白的去乙酰化作用。
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FMK_9a_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Jun.-08-2017Print Date:Jun.-08-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :FMK 9aCatalog No. :HY-100522CAS No. :1955550-51-21.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:FMK–9a; FMK9aFormula:C23H21FN2O3Molecular Weight:392.42CAS No. :1955550-51-24. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
PF-06409577_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PF–06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC 50 of 7 nM.IC50 & Target: EC50: 7 nM (AMPK α1β1γ)[1]In Vitro: PF–06409577 possesses similar potency toward the human and rat α1β1γ1 isoforms. In broad panel screening against other receptors, channels, PDEs and kinases, PF–06409577 exhibits minimal off–target pharmacology. PF–06409577 shows no detectable inhibition of hERG in a patch–clamp assay (100 μM) and is not an inhibitor (IC 50>100 μM) of the microsomal activities of major human cytochrome P450 isoforms [1].In Vivo: PF–06409577 demonstrates moderate plasma clearance in rats, dogs, and monkeys, and is well distributed with steady state distribution volume. Following oral administration of crystalline PF–06409577 in 0.5% methylcellulose suspension, PF–06409577 is rapidly absorbed in rats, dogs, and monkeys. The corresponding oral bioavailability values in rats, dogs, and monkeys, are 15%, 100%,and 59%, respectively. Dose responsive increases in pAMPK relative to total AMPK (tAMPK) in whole kidney tissue are observed with a maximal 3.8–fold response at 300 mg/kg PF–06409577 treatment [1]. Oral administration of PF–06409577 (10, 30, and 100 mg/kg QD)results in dose–dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2–fold reduction in 24–hour urinary albumin loss compared to vehicle control after 60 days of treatment [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]PF–06409577 is prepared in DMSO. PF–06409577 is incubated with fully phosphorylated AMPK in assay buffer atroom temperature for 15 min followed by addition of PP2a and another incubation for 60 min at room temperature. The phosphatase treatment is quenched and the kinase assay initiated with the addition of okadaic acid (50 nM final), 50 nM Cy–5 SAMS peptide and ATP equal to Km for each isoform. Reactions are incubated for an additional 60 min and the kinase reaction is quenched with the addition of 10 mM EDTA and 2 nM Eu–pACC antibody in detection Buffer. Kinase activity is monitored by excitation at 320 nM and measuring emission at 665 and 615 nM, respectively [1].Animal Administration: PF–06409577 is prepared in 0.5% methylcellulose [1].[1]Rat: Daily administration of 0.5% methylcellulose (p.o.),PF–06409577 at 10, 30, or 100 mg/kg (p.o.), PF– 249 at 3, 10, or 30 mg/kg (p.o.), or ramipril in drinking water (1 mg/kg/day) is initiated and continued for 68 days. Urine is collected for 24–hours and volume recorded from all lean and obese rats after 14, 28, 42, and 60days of dosing. On Day 63 all rats are administered a final dose after 16–hour overnight fasting. One hour following the final dose,blood glucose is measured by glucometer and a 100 μL tail vein blood sample collected and processed for determination of insulin levels and total protein. Each rat is then anesthetized with isoflurane. The right kidney is collected and immediately freeze–clamped and transferred to liquid nitrogen storage; the left kidney is fixed in 10% formalin. Rats are then euthanized by exsanguination from the vena cava [1]Product Name:PF–06409577Cat. No.:HY-103683CAS No.:1467057-23-3Molecular Formula:C19H16ClNO3Molecular Weight:341.79Target:AMPK Pathway:Epigenetics; PI3K/Akt/mTOR Solubility:DMSO: ≥100 mg/mLReferences:[1]. Cameron KO, et al. Discovery and Preclinical Characterization of 6–Chloro–5–[4–(1–hydroxycyclobutyl)phenyl]–1H–indole–3–carboxylic Acid(PF–06409577), a Direct Activator of Adenosine Monophosphate–activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy. J Med Chem. 2016 Sep 8;59(17):8068–81.[2]. Salatto CT, et al. Selective Activation of AMPK β1–Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy. J Pharmacol Exp Ther. 2017 May;361(2):303–311.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
CWHM-12_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:CWHM–12 is a potent inhibitor of αV integrins with IC 50s of 0.2, 0.8, 1.5, and 1.8 nM for αvβ8, αvβ3, αvβ6, and αvβ1.IC50 & Target: IC50: 0.2 nM (αvβ8), 0.8 nM (αvβ3), 1.5 nM (αvβ6), 1.8 nM (αvβ1), 61 nM (αvβ5)[1]In Vitro: CWHM–12 (CWHM 12) also less potently inhibits αvβ5 (IC 50=61 nM) and αIIbβ3/α2β1/α10β1 (IC 50>5000 nM). CWHM–12demonstrates high potency against all of the five possible β subunit binding partners (αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8) in in vitro ligand–binding assays, with somewhat less potency against αvβ5 than against the other αv integrins [1].In Vivo: Mice are treated with CCl 4 for 3 weeks to establish fibrotic disease and then treated with CWHM–12 (CWHM 12) or vehicle for the final 3 weeks of CCl 4. CWHM–12 significantly reduces liver fibrosis even after fibrotic disease have been established.Digital image quantitation demonstrates significantly reduced p–SMAD3 signaling in the livers of CWHM–12 treated micecompare to controls, demonstrating that the protection from CCl 4–induced hepatic fibrosis observed in CWHM–12 treated mice is due at least in part to a reduction in TGF–β activation by αv integrins. Besides, administration of CWHM–12 significantly inhibited progression of pulmonary fibrosis [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Functions of integrins αvβ1, αvβ8, α2β1 and α10β1 are measured using cell–free receptor–ligand interaction assays using purified recombinant human integrins. Ligands used are human fibronectin for αvβ1, human LAP for αvβ8, bovine collagen II for α2β1, and murine laminin I for α10β1. 96–well plates are coated with the predetermined optimal concentration of ligand overnight, washed 3X with TBS+++ (25 mM Tris pH7.4, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl 2, 1 mM MnCl 2, 1mM CaCl 2), andblocked with TBS+++/1%BSA. Purified integrin is diluted in TBS+++/0.1%BSA with or without compounds (e.g., CWHM–12), and the solution added to empty wells of the washed ligand–coated plate according to a standard template, with each sample repeated in triplicate. After incubation for 2 hr at room temperature, the plate is washed 3X with TBS+++. Biotin–labeled antibody against the αv subunit (αvβ1, αvβ8 assays) or β1 subunit (α2β1, α10β1 assays) is applied for 1 hr. The plate is washed 3X with TBS/0.1%BSA.Streptavidin–conjugated horseradish peroxidase is added to the wells, and the plate incubated for 20 min at room temperature.Following a 3X TBS+++ wash, bound integrin is detected using streptavidin–conjugated horseradish peroxidase and TMB substrate with absorbance measured at 650 nm. For assay of αIIbβ3 (IIbIIIa) function, plates are coated with the purified human integrinovernight, washed 3X with TBS+++, and blocked with TBS+++/1%BSA. Alexa Fluor647–labeled purified human fibrinogen is diluted in TBS+++/0.1%BSA with or without compounds, and the solutions are added to the integrin–coated plate. After 2 hr incubation,the plate is washed 3X with TBS+++, and bound ligand is detected by absorbance measured at 640/668nm. For all assays,concentration–response curves are constructed by non–linear regression analysis and IC 50 values are calculated using GraphPad Prism software [1].Cell Assay: CWHM–12 (CWHM 12) is solubilized in DMSO and stored, and then diluted with appropriate media before use [1].[1]The stably transfected human 293 cells over–expressing human αvβ3 or αvβ5 are pre–incubated in HBSS buffer containing 200 μM MnCl 2Product Name:CWHM–12Cat. No.:HY-18644CAS No.:1564286-55-0Molecular Formula:C 26H 32BrN 5O 6Molecular Weight:590.47Target:Integrin Pathway:Cytoskeleton Solubility:DMSO: 10.5 mg/mLfor 30 min at 37°C with 3–fold dilutions of compound (e.g., CWHM–12). Each sample is then added to triplicate wells of a 96–well plate which has been coated overnight at 4°C with a predetermined optimal concentration of purified vitronectin, washed, blocked by 1 hr incubation with BSA, and washed again. Cells are allowed to attach for 30 min at 37°C, and non–adherent cells are removed by washing. Remaining attached cells are measured by endogenous alkaline phosphatase activity using para–nitrophenyl phosphate and reading absorbance signal at 405 nM. The same procedure is used to measure adhesion of αvβ6–expressing human HT–29 cells to purified human latency associated peptide, and α5β1–expressing human K562 cells to human plasma fibronectin. In all cell–based assays, binding by the expected integrin is verified by testing activity of corresponding isotype–matched positive (function–blocking) and negative control antibodies[1].Animal Administration: CWHM–12 (CWHM 12) is solubilized in 50% DMSO (in sterile water) (Mice)[1].[1]Mice[1]The mTmG (Td tomato/EGFP) and Ai14 (Rosa–CAG–LSL–tdTomato–WPRE) mice are used and crossed with Pdgfrb–Cre mice. Wild type C57/BL6 mice, Itgav flox/flox mice and itgb8flox/flox mice are used. Mice used for all experiments are 8–12 weeks old and are housed under specific pathogen–free conditions. For all studies CWHM–12 and CWHM–96 are solubilized in 50% DMSO (insterile water) and dosed to 100 mg/kg/day. Drug or vehicle (50% DMSO) are delivered by implantable ALZET osmotic minipumps. For CCl4–induced fibrosis, pumps are inserted subcutaneously either before the firReferences:[1]. Henderson NC, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013 Dec;19(12):1617–24.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
MK-0974_781649-09-0_DataSheet_MedChemExpress
Product Name:MK-0974CAS No.:781649-09-0Cat. No.:HY-32709Product Data SheetMWt:566.52Formula:C26H27F5N6O3Purity :>98%Solubility:DMSOy Mechanisms:Biological Activity:MK 0974(Telcagepant)is a highly potent selective and orally bioavailable CGRP receptorPathways:GPCR/G protein; Target:CGRP ReceptorPathways:Neuronal Signaling; Target:CGRP Receptor MK-0974(Telcagepant) is a highly potent, selective, and orally bioavailable CGRP receptor antagonist with Ki values of 0.77 nM and 1.2 nM for human and rhesus CGRP receptorsrespectively; displays >1500-fold lower affinity for the canine and rat receptors.IC50 value: 0.77/1.2 nM(Human and rhesus CGRP) [1]Target: CGRP receptor in vitro: MK-0974 is a potent antagonist of the human (K(i) = 0.77 nM) and rhesus (K(i) = 1.2 nM)CGRP receptors but displays >1500-fold lower affinity for the canine and rat receptors asdetermined via (125)I-human CGRP competition binding assays [1]. [(3)H]MK-0974 displayed reversible and saturable binding to both SK-N-MC membranes and rhesus cerebellum with a K(D) of References:[1]. Salvatore CA, et al. Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide g ()1.9 nM and 1.3 nM, respectively [2].in vivo: In monkeys, MK-0974 displayed moderate clearance (14-20 ml min(-1) kg(-1)), while oral bioavailability was 6%. The pharmacokinetic...]py y )p p ]p y g p preceptor antagonist for the treatment of migraine. J Pharmacol Exp Ther. 2008 Feb;324(2):416-21.[2]. Moore EL, et al. Examining the binding properties of MK-0974: a CGRP receptor antagonist forthe acute treatment of migraine. Eur J Pharmacol. 2009 Jan 14;602(2-3):250-4.[3]. Roller S, et al. Preclinical pharmacokinetics of MK-0974, an orally active calcitonin-gene related peptide (CGRP)-receptor antagonist, mechanism of dose dependency and species differences.Xenobiotica. 2009 Jan;39(1):33-45....Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18 W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。
KU-0063794_938440-64-3_DataSheet_MedChemExpress
Product Name:KU-0063794CAS No.:938440-64-3Product Data SheetCat. No.:HY-50710MWt:465.54Formula:C25H31N5O4Purity :>98%Solubility:Mechanisms:Biological Activity:Pathways:PI3K/Akt/mTOR ; Target:mTOR DMSO ≥10mg/mL Water <1.2mg/mL Ethanol <1.2mg/mLg y KU-0063794 is a selective inhibitor of mammalian target of rapamycin (mTOR) (IC50 ~10 nM formTORC1 and mTORC2 respectively); no effect on PI3Ks.IC50 value: ~10 nM [1]Target: mTORC1/C2KU-0063794 displays no activity at PI 3-kinase or 76 other kinases tested. Inhibits activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK. KU-0063794 suppresses cell growth and induces G1 cell cycle arrest in vitro.References:[1]. Garcia-Martinez et al Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin(mTOR). Biochem.J. (2009)421 29.[2]. Collak FK, Yagiz K, Luthringer DJ, Erkaya B, Cinar B.Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the y p p g p y p y g gantitumor activity of mammalian sterile 20-like kinase 1.J Biol Chem. 2012 Jul 6;287(28):23698-709.Epub 2012 May 22.[3]. Wahdan-Alaswad RS, Bane KL, Song K, Shola DT, Garcia JA, Danielpour D.Inhibition ofmTORC1 kinase activates Smads 1 and 5 but not Smad8 in human prostate cancer cells, mediatingcytostatic response to rapamycin.Mol Cancer Res. 2012 Jun;10(6):821-33. Epub 2012 Mar 27.[4]. Haagensen EJ, Kyle S, Beale GS, Maxwell RJ, Newell DR.The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.Br J...Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。
CMX001_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:CMX001 (Brincidofovir; HDP–CDV) was developed as an orally active, lipophilic form of cidofovir (CDV); has enhanced activity in vitro and in vivo compared to CDV against certain herpesviruses, adenoviruses and orthopoxviruses.IC50 Value: 5.5 nM (EC50, in PDA at 7 dpi) [3]Target: anti–CMVCMX001 is currently in Phase II clinical studies for development as a therapeutic agent for human CMV, adenovirus and BK virus infections, as well as, for adverse events following smallpox vaccinations.in vitro: In PDA at 7 dpi, the CMX001 50% effective concentration (EC50) was 5.55 nM, the 50% cytotoxic concentration (CC50) was 184.6 nM, and the 50% selectivity index (SI50) was 33.3. The EC90 was 19.7 nM, the CC90 was 5,054 nM, and the SI90 was 256.1. In COS–7 cells, JCV replication was faster and the EC50 and EC90 were 18– and 37–fold higher than those in PDA, i.e., 0.1 μM and 0.74μM (CC50, 0.67 μM; SI50, 6.7; CC90, 12.2 μM; SI90, 16.5) at 5 dpi [3].in vivo: CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra–nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other–day for 14 days provided solid protection against mortality and weight loss following an intra–nasal challenge of(100–200) x LD(50) of ectromelia virus [1]. When CMX001 was administered orally to mice infected with HSV–1, mortality was reduced significantly (p≤0.001) with all three dose levels when treatments were initiated 24 h post viral inoculation. When treatments were started 48 h post viral inoculation, 5 and 2.5 mg/kg significantly reduced mortality (p≤ 0.001). If treatments were delayed until 72 h post viral inoculation, CMX001 did not reduce mortality or increase the mean day to death. When mice were infected intranasally with HSV–1 and treatments initiated 24 h post viral inoculation using CMX001 at 5 mg/kg or ACV at 100 mg/kg, virus replication in target organs was reduced by both CMX001 and ACV when compared to vehicle treated mice [2].Toxicity: Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose–limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed [4].References:[1]. Parker S, et al. Efficacy of therapeutic intervention with an oral ether–lipid analogue of cidofovir (CMX001) in a lethal mousepox model. Antiviral Res.2008 Jan;77(1):39–49.[2]. Quenelle DC, et al. Efficacy of CMX001 against herpes simplex virus infections in mice and correlations with drug distributionstudies. J Infect Dis. 2010Nov 15;202(10):1492–9.[3]. Gosert R, et al. CMX001 (1–O–hexadecyloxypropyl–cidofovir) inhibits polyomavirus JC replication in human brain progenitor–derived astrocytes.Antimicrob Agents Chemother. 2011 May;55(5):2129–36.[4]. Marty FM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic–cell transplantation. N Engl J Med. 2013 Sep 26;369(13):1227–36.Product Name:CMX001Cat. No.:HY-14532CAS No.:444805-28-1Molecular Formula:C 27H 52N 3O 7P Molecular Weight:561.69Target:CMV Pathway:Anti–infection Solubility:10 mM in DMSOCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
PIK-93_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PIK–93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC 50 of 19 nM, and also inhibits PI3Kα with IC 50 of 39 nM.IC50 & Target: IC50: 19 nM (PI4KIIIβ), 39 nM (PI3Kα)In Vitro: PIK–93 inhibits PI3Kγ and PI4KIIIβ, with IC 50 values of 16 nM and 19 nM, respectively. PIK–93 also inhibits other members of PI3Ks, including PI3Kα, β, and δ, with IC 50 values of 39 nM, 0.59 μM, and 0.12 μM, respectively. PIK–93 shows no obvious inhibitory effect against a panel of other kinases, even at a concentration of 10 μM [1]. In differentiated HL60 (dHL60) cells, PIK–93 (0.5 μM–1μM) impairs consolidation and stability of the leading edge formed after treatment with uniform f–Met–Leu–Phe (fMLP). PIK–93alters the localization, but not the amount, of the fMLP–dependent accumulation of total F–actin. In fMLP gradients, PIK–93 reduces the chemotactic index and triples the cells' turning frequency [2]. In COS–7 cells, PIK–93 (250 nM) effectivelyabrogates the accumulation of CERT–PH domain and FL–Cer in Golgi. PIK–93 of the same concentration alsosignificantly inhibits the conversion of [3H]serine–labeled endogenous ceramide to sphingomyelin. These facts indicate a key role of PI4KIIIβ in ceramide transport between the ER and Golgi, as well as in the regulation of spingomyelin synthesis [3]. In T6.11 cells,PIK–93 (300 nM) reduces carbachol–induced translocation of TRPC6 to the plasma membrane and net Ca 2+ entry [4]. A recent reportshows that PIK–93 has anti–enterovirus effects, as revealed by its inhibition of both poliovirus (PV) and hepatitis C virus (HCV)replication, with EC 50 values of 0.14 μM and 1.9 μM, respectively [5]. PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]IC 50 values are measured using a standard TLC assay for lipid kinase activity. Kinase reactions are performed by preparing areaction mixture containing kinase, PIK–93 (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl 2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ–32P–ATP to a final concentration 10 or 100 μM, and allowed to proceed for 20 min at room temperature. For TLC analysis,reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl 3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase transferred to a new tube using a gel loading pipette tip precoated with CHCl 3.This extract is spotted on TLC plates and developed for 3 hours–4 hours in a 65:35 solution of n–propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen, and quantitated. Kinase activity is typically measured at 10–12concentrations of PIK–93 representing two–fold dilutions from the highest concentration of 100 μM.Cell Assay:[1]For actin staining, dHL60 cells are preincubated in suspension with PIK–93 or vehicle for 40 min, centrifuged for 5 min at 2000 rpm at room temperature in a J6–B centrifuge, resuspended in mHBSS containing the respective agent at the sameconcentration, allowed to stick to fibronectin–covered coverslips, and subjected to stimulation with a uniform concentration of 100nM f–Met–Leu–Phe (fMLP) for 3 min. Cells are fixed in 3.7% PFA and stained with 10 units/mL rhodamine–phalloidin for 15 min.Product Name:PIK–93Cat. No.:HY-12046CAS No.:593960-11-3Molecular Formula:C 14H 16ClN 3O 4S 2Molecular Weight:389.88Target:PI4K; PI3K Pathway:PI3K/Akt/mTOR; PI3K/Akt/mTOR Solubility:10 mM in DMSOReferences:[1]. Knight ZA, et al. A pharmacological map of the PI3–K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733–47.[2]. Van Keymeulen A, et al. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J Cell Biol. 2006 Jul 31;174(3):437–45.[3]. Toth B, et al. Phosphatidylinositol 4–kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem. 2006 Nov 24;281(47):36369–77.[4]. Monet M, et al. Involvement of phosphoinositide 3–kinase and PTEN protein in mechanism of activation of TRPC6 protein in vascular smooth muscle cells. J Biol Chem. 2012 May 18;287(21):17672–81.[5]. Arita M, et al. Phosphatidylinositol 4–kinase III beta is a target of enviroxime–like compounds for antipoliovirus activity. J Virol. 2011 Mar;85(5):2364–72.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
GDC-0623_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:GDC–0623 is a potent, ATP–uncompetitive inhibitor of MEK1 (K i =0.13 nM, +ATP), and displays 6–fold weaker potency against HCT116 (KRAS (G13D), EC 50=42 nM) versus A375 (BRAF V600E , EC 50=7 nM).IC50 & Target: Ki: 0.13 nM (MEK1,+ATP)In Vitro: DC–0623 and G–573 are able to prevent MEK phosphorylation by CRAF in vitro, and able to block MEK phosphorylation by BRAF(V600E)[1]. GDC–0623 is potent, ATP–uncompetitive inhibitors of MEK1 but shows distinct shifts in cellular activity compared with the other two inhibitors, only 6–fold half–maximum effective concentration (EC 50) decreases [2].In Vivo: GDC–0623 (40 mg/kg, p.o.) shows percent tumour growth inhibition (%TGI) in MiaPaCa–2 xenograft model. GDC–0623 andG–573 show superior antitumour activity compared to GDC–0973 in all three KRAS models [1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]0.14 μM of purified inactive recombinant MEK–1 protein ispreincubated with inhibitors in 15 μL of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 100 μM ATP, 15 mM MgCl 2). After incubating 10 minutes at 30°C, 1 ng of BRAF, CRAF or BRAF V600E combined with 0.5 μg of inactive recombinant ERK2 isadded to the reaction in total volume of 20 μL. After incubating 30 minutes at 30°C the reaction isstopped by adding LaemmLe sample buffer. Enzyme activity is measured by determining level of phosphor–MEK by SDS–PAGE. Immunoreactive proteins are visualized with SuperSignal West Pico Chemiluminescent Substrate.Cell Assay:[1]Flag–MEK1 mutants, S212P and S212A, are generated using the QuickChange site directed mutagenesis kit. Mammalian expression vectors for N–terminal Flag tagged MEK–1 are expressed in HCT116 cells. 1.8×106 HCT116 cells are plated in 10 cm plate and transfected on the following day with 17 μg of expression constructs using lipofectamine 2000. After 48 hours cells are treated with inhibitors for the indicated times, harvested and lysed in 100 μL cell extraction buffer. Cell lysates from each sample are analyzed by SDS–PAGE. Membranes are incubated with phospho–MEK S221, phospho–ERK1/2 and MEK1 primary antibodies andimmunoreactive proteins are analyzed by SuperSignal West Pico Chemiluminescent Substrate.Animal Administration: GDC–0623 is dissolved in methylcellulose 0.1% tween 80 0.1% (MCT).[1]Colo205 xenografts are established by inoculating 5×106 cells resuspended in Hank's Balanced Salt Solution (HBSS) subcutaneously (s.c.) in the rear right flank of 6–8 week old female nude (nu/nu) mice. NCI–H2122 xenografts are established by inoculating 1×107 cells resuspended in Hank's Balanced Salt Solution (HBSS) plus matrigel (growth factor reduced) s.c. in the rear right flank of 6–8 week old female nu/nu mice. Both A375 and MiaPaca–2 xenografts are initiated by transplanting 1 mm 3 tumor fragments from their respective passaged tumors s.c. into the flank of athymic nu/nu mice. When tumors reached appr 200 mm 3, mice are randomized and treated with daily (QD) oral gavage (PO) with either vehicle [methylcellulose 0.1% tween 80 0.1% (MCT)], GDC–0973 (at 10 mg/kg), GDC–0623 (40 mg/kg), or G–573 (100 mg/kg). All doses of MEK inhibitors represented maximal tolerated doses (MTDs), resulting in no more than 15–20% body weight loss. TumorProduct Name:GDC–0623Cat. No.:HY-15610CAS No.:1168091-68-6Molecular Formula:C 16H 14FIN 4O 3Molecular Weight:456.21Target:MEK Pathway:MAPK/ERK Pathway Solubility:DMSO: ≥ 30 mg/mLvolumes are determined using digital calipers using the formula (L×W×W)/2. Tumor growth inhibition (%TGI) iscalculated as the percentage of the area under the fitted curve (AUC) for the respective dose group per day in relation to the vehicle. Animal weights are recorded twice per week and mice are removed from study if body weights dropped ≥20%. Partial responses (PRs) are defined as any tumor demonstrating a ≥ 50% decrease in tumor volume, whereas complete responses (CRs) are defined as any tumor demonstrating 100% reduction in tumor volume at any point during the study.References:[1]. Hatzivassiliou G, et al. Mechanism of MEK inhibition determines efficacy in mutant KRAS– versus BRAF–driven cancers. Nature. 2013 Sep 12;501(7466):232–6.[2]. Takahashi RH, et al. Elucidating the Mechanisms of Formation for Two Unusual Cytochrome P450–Mediated Fused Ring Metabolites of GDC–0623, a MAPK/ERK Kinase Inhibitor. Drug Metab Dispos. 2015 Dec;43(12):1929–1933.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
ML402_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:ML402 is a selective TREK–1 activator.IC50 & Target: TREK–1[1]In Vitro: Xenopus oocyte two–electrode voltage–clamp measurements show that ML335 and ML402 activate K 2P 2.1 and K 2P 10.1 but not K 2P 4.1(14.3±2.7 μM, K 2P 2.1–ML335; 13.7±7.0 μM, K 2P 2.1–ML402; 5.2±0.5 μM, K 2P 10.1–ML335; and 5.9±1.6 μM, K 2P 10.1–ML402).The K 2P modulator pocket has a single difference among TREK subfamily members at the cation–π interaction position, K 2P 2.1 Lys271,which is also a lysine in K 2P 10.1 but a glutamine in K 2P 4.1.Swapping the Lys271 equivalent between K 2P 2.1 and K 2P 4.1 results in a clear phenotype reversal for ML335 and M402 activation. K 2P 2.1 (K271Q) is insensitive to ML335 and ML402, whereas K 2P 4.1 (Q258K) responds to both with a similar EC 50 to K 2P 2.1 (14.3±2.7 μM, K 2P2.1–ML335; 16.2±3.0 μM, K 2P4.1(Q258K)–ML335; 13.7±7.0 μM, K 2P 2.1–ML402; 13.6±1.5 μM, K 2P 4.1 (Q258K)–ML402) but with a lower magnitude response than K 2P 2.1[1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]K 2P 2.1cryst ML335 and ML402 complex crystals grow in the same conditions as K 2P 2.1cryst , but the protein is incubated for at least 1 h with 2.5 mM of activator (including ML 402) before setting the crystal plates. ML335 and ML402 are insoluble inaqueous solutions, so they are dissolved in 100% DMSO at a concentration of 500 mM. Then each compound is diluted 1:100 in SEC buffer to 5 mM concentration, giving a milky solution. This solution is mixed 1:1 to K 2P 2.1cryst previously concentrating to 12 mg/mL.The K 2P 2.1cryst ML402 mixture results in a clear solution, while the mixture with ML335 is slightly milky. The samples are brieflycentrifuged in a table–top centrifuge (10,000×g) to remove any insoluble material before setting the crystal plates. Dose–response experiments are carried by first preparing a DMSO stock solution of each activator (including ML402) at a concentration of 100 mM.Owing to the low solubility of the compounds the highest test concentrations in recording solution are 100 μM and 80 μM for ML335and ML402, respectively. Other concentrations are prepared by serial dilutions of the 100 μM solution in recording buffersupplementing with 0.1% DMSO [1].References:[1]. Lolicato M, et al. K2P2.1 (TREK–1)–activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017 Jul 20;547(7663):364–368.Product Name:ML402Cat. No.:HY-104027CAS No.:298684-44-3Molecular Formula:C14H14ClNO2S Molecular Weight:295.78Target:Potassium Channel Pathway:Membrane Transporter/Ion Channel Solubility:DMSO: 150 mg/mLCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
Emamectin_Benzoate_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:Emamectin Benzoate works as a chloride channel activator by binding gamma aminobutyric acid (GABA) receptor andglutamate–gated chloride channels disrupting nerve signals within arthropods.Target: GABA ReceptorEmamectin Benzoate stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA's affinity for its receptor on the post–junction membrane of muscle cells in insects and arthropods.PROTOCOL (Extracted from published papers and Only for reference)Animal administration [1]Emamectin benzoate was dissolved in acetone to various concentrations (200, 100, 50, 25, 10, 5.0 and 1.0 mg a.i./L). The nematicidal efficacy of Emamectin benzoate against J2 of M. incognita was determined in aqueous tests. Emamectin benzoate treatments (200,100, 50, 25, 10, 5.0 and 1.0 mg a.i./L) were prepared in acetone + distilled water (10: 90% by volume), and distilled water, as well as a mixture of water with acetone at concentrations equivalent to those in the treatment wells, were used as controls. Then 1 mL ofsolution and 1 mL of root–knot nematodes J2 (containing average 150 J2) was added to each well of a 24–well plate. Well plates were wrapped with parafilm, placed in plastic zip–lock bags and stored in aluminum foil pans covered with another pan to keep them dark.Units were kept at 25°C. After 48 h, the relative percentages of the motile and immotile J2 were evaluated using an invertedmicroscope at 40×magnification. Furthermore, nematodes were moved to distilled water after washing in tap water through a 20 μm pore screen to remove excess chemicals. To confirm the nematicidal activity of emamectin benzoate, immobile 30 J2 from each treatment were collected from the above experiments, transferred to tissue culture plates filled with water, and monitored for 12 h.The experiments had five replications and were repeated three times.References:[1]. Cheng X, et al. Effect of Emamectin Benzoate on Root–Knot Nematodes and Tomato Yield. PLoS One. 2015 Oct 28;10(10):e0141235.Product Name:Emamectin (Benzoate)Cat. No.:HY-B0837CAS No.:155569-91-8Molecular Formula:C 104H 154N 2O 28Molecular Weight:1880.33Target:GABA Receptor; GABA Receptor Pathway:Neuronal Signaling; Membrane Transporter/Ion Channel Solubility:DMSO: ≥ 31 mg/mLCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@ Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
MK-8033_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:MK8033 is a novel and specific dual ATP competitive c–Met/Ron inhibitor (IC50=1 nM Wt c–Met) under investigation as a treatment for cancer.IC50 Value: 1 nM (Wt c–Met); 2.0 nM (c–Met N1100Y) [1]Target: c–Met/Ronin vitro: MK–8033 binds 3–fold more tightly to phosphorylated c–Met kinase domain (Kd= 3.2 nM) than to its unphosphorylatedcounterpart (Kd = 10.4 nM). Signigicantly, MK–8033 potently inhibits kinase activity of three oncogenic c–Met activation loop mutants,Y1230C, Y1230H, and Y1235D (IC50s ranging from 0.6 to 1 nM at 50 uM ATP) in addition to other c–Met activating mutants N1100Y and M1250T. MK–8033 potently inhibited GTL–16 proliferation with an IC50 of 582 ± 30 nM. By contrast the HCT116 cell line, which does not harbor basal c–Met activation, was not inhibited by MK–8033 (IC50 > 10000 nM) [1]. MK–8033 radiosensitized thehigh–c–Met–expressing EBC–1 and H1993 cells but not the low–c–Met–expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c–Met protein at 30 minutes after the irradiation. Subsequent targeting of thisup–regulated c–Met by using MK–8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460cells. MK–8033reduced the levels of radiation–induced phosphorylated (activated) c–Met in A549 cells [2].in vivo: MK–8033 was orally dosed in GTL–16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p–Met (Y1349) in tumors and MK–8033 concentrations in plasma. At 100 mg/kg,essentially complete inhibition of p–Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK–8033 level and Met pY1349. Treatment with escalating dosed of MK–8033 for 21 days lead to antitumor efficacies in a dose–dependent manner. Dosing at 3, 10, 30, and 100mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to tumor from vehicle–treated mice.signatures.PROTOCOL (Extracted from published papers and Only for reference)Cell assay [2]For this assay, 200,000 cells were plated on coverslip placed in 35–mm dish and allowed to attach overnight. Then cells were irradiated (4Gy) and 2 h later exposed to 10 μM MK–8033 for 24 h. After the incubation period, cells were again irradiated (4 Gy) and incubated for upto 6 hours. Then, the cells were fixed with 1% paraformaldehyde for 10 min followed by ethanol (70%) fixation for 10 minutes at room temperature. The cells were then treated with 0.1% NP40 in PBS for 20 min, washed in PBS four times and then blocked with 5%bovine serum albumin in PBS for 30 min. The cells were then incubated with anti–γ–H2AX (Millipore) antibody in 5% bovine serum albumin in PBS overnight. Next day, cells were incubated with FITC–labeled secondary antibody at a dilution of 1:300 (?–H2AX) in 5%BSA in PBS for 30 min. Cells then were incubated in the dark with 4 4′,6–diamidino–2–phenylindole (DAPI, 1 mg/mL) in PBS for 5 min,and coverslips were mounted on a slide with an antifade solution (Molecular Probes). Slides were examined using a Leica fluorescence microscope, and images were captured by a CCD camera and imported into Advanced Spot Image analysis software package. ForProduct Name:MK–8033Cat. No.:HY-13299CAS No.:1001917-37-8Molecular Formula:C 25H 21N 5O 3S Molecular Weight:471.53Target:c–Met/HGFR Pathway:Protein Tyrosine Kinase/RTK Solubility:DMSO: ≥ 46 mg/mLeach treatment condition, the number of γ –H2AX foci were determined in at least 50 cells [14].References:[1]. Northrup AB, et al, Discovery of1–[3–(1–methyl–1H–pyrazol–4–yl)–5–oxo–5H–benzo[4,5]cyclohepta[1,2–b]pyridin–7–yl]–N–(pyridin–2–ylmethyl)methanesulfonamide (MK–8033): A Specific c–Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c–Met. J Med Chem. 2013 Mar 28;56(6):2294–310.[2]. Bhardwaj V, et al. C–Met inhibitor MK–8003 radiosensitizes c–Met–expressing non–small–cell lung cancer cells with radiation–induced c–Met–expression. J Thorac Oncol. 2012 Aug;7(8):1211–7.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
MK-0974_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:MK–0974 is a highly potent, selective, and orally bioavailable CGRP receptor antagonist with K i values of 0.77 nM and 1.2 nM for human and rhesus CGRP receptors, respectively, but displays > 1500–fold lower affinity for the canine and rat receptors.IC50 & Target: Ki: 0.77 nM (human CGRP), 1.2 nM (rhesus CGRP)In Vitro: MK–0974 displays affinity (K i ) for the canine and rat receptors, with values of 1204 nM and 1192 nM (n=10), respectively.MK–0974 potently blocks human α–CGRP–stimulated cAMP responses in human CGRP receptor expressing HEK293 cells with an IC 50of 2.2 nM [1]. MK–0974 displays saturable binding to SK–N–MC membranes with a K D of 1.9 nM and B max of 479 fmol/mg protein.MK–0974 also displays saturable binding to rhesus cerebellum homogenate with a K D</sub of 1.3 nM and Bmax of 20 fmol/mg [2].In Vivo: MK–0974 (i.v. bolus, 1 mg/kg) demonstrates that the efficacy of this antagonist is time–dependent and correlated with plasma levels [1]. The pharmacokinetics of MK–0974remains linear across 0.5–10 mg/kg intravenous dose in monkeys, but the oral area under the plasma concentration–time curve (AUC) increase (5–30 mg/kg) is 15–fold overdose–proportional [3].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay:[1]HEK293 cells stably transfected with CLR/RAMP1 are plated in complete growth medium at 85,000 cells/well in96–well poly–D–lysine–coated plates and cultured for 19 h before assay. Cells are washed with PBS and then incubated withinhibitor in the presence or absence of 50% human serum for 30 min at 37°C and 95% humidity in Cellgro CompleteSerum–Free/Low–Protein medium with L–glutamine and 1 g/L bovine serum albumin. Isobutylmethylxanthine is added to thecells at a concentration of 300 μM and incubated for 30 min at 37°C. Human α–CGRP is added to the cells at a concentrationof 0.3 nM and allowed to incubate at 37°C for 5 min. After α–CGRP stimulation, the cells are washed with PBS and processedfor cAMP determination using the two–stage assay procedure according to the manufacturer's recommended protocol.Dose–response curves are plotted, and IC 50 values are determined.Animal Administration:[1]Rhesus monkeys (male and female) weighing between 4 and 10 kg are anesthetized initially with ketamine (0.1 mL/kg i.m.) and then placed in the supine position on a temperature–controlled water circulating blanket and intubated with a 3–mm tracheal tube connected to 1–liter oxygen/1 to 2% isoflurane gas anesthesia. The right saphenous vein is cannulated forintravenous drug delivery, and blood samples are obtained from the left saphenous artery. Four rubber O–rings (8 mm inner diameter)are placed on the ventral side of the forearm without directly being positioned over a visible vessel.References:[1]. Salvatore CA, et al. Pharmacological characterization of MK–0974[N–[(3R,6S)–6–(2,3–difluorophenyl)–2–oxo–1–(2,2,2–trifluoroethyl)azepan–3–yl]–4–(2–oxo–2,3–dihydro–1H–imidazo[4,5–b]pyridin–1–yl)piperidine–1–carboxamide],a potent and orally active calcitoProduct Name:MK–0974Cat. No.:HY-32709CAS No.:781649-09-0Molecular Formula:C 26H 27F 5N 6O 3Molecular Weight:566.52Target:CGRP Receptor; CGRP Receptor Pathway:GPCR/G Protein; Neuronal Signaling Solubility:10 mM in DMSO[2]. Moore EL, et al. Examining the binding properties of MK–0974: a CGRP receptor antagonist for the acute treatment of migraine. Eur J Pharmacol. 2009 Jan 14;602(2–3):250–4.[3]. Roller S, et al. Preclinical pharmacokinetics of MK–0974, an orally active calcitonin–gene related peptide (CGRP)–receptor antagonist, mechanism of dose dependency and species differences. Xenobiotica. 2009 Jan;39(1):33–45.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
BIO_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:BIO is a potent and selective inhibitor of GSK–3 and CDK1–cyclinB complex with IC 50s of 5 nM/320 nM/83 nM forGSK–3αβ/CDK1/CDK5, respectively.IC50 & Target: IC50: 5 nM (GSK–3αβ), 320 nM (CDK1), 83 nM (CDK5)In Vitro: BIO is a specific inhibitor of glycogen synthase kinase–3 (GSK–3), with IC 50 of 5 nM for GSK–3α/β, shows > 16–fold selectivity over CDK5. BIO interacts within the ATP binding pocket of these kinases, reduces β–catenin phosphorylation on aGSK–3–specific site in cellular models, closely mimicks Wnt signaling in Xenopus embryos [1]. In human and mouse embryonic stem cells, BIO maintains the undifferentiated phenotype and sustains expression of the pluripotent state–specific transcription factors Oct–3/4, Rex–1 and Nanog. BIO–mediated Wnt activation is functionally reversible, as withdrawal of the compound leads to normal multidifferentiation programs in both human and mouse embryonic stem cells [2]. BIO promotes proliferation in mammalian cardiomyocytes [3]. 6BIO is also a pan–JAK inhibitor, with IC 50 values of 0.03, 1.5, 8.0, 0.5 μM for TYK2, JAK1, JAK2 and JAK3,respectively. BIO selectively inhibits phosphorylation of STAT3 and induces apoptosis of human melanoma cells [4].In Vivo: BIO (50 mg/kg, p.o.) suppresses melanoma tumor growth in a mouse xenograft model [4].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Kinase activities are assayed in Buffer A or C at 30°C, at a final ATP concentration of 15 μM. Blank values aresubtracted and activities calculated as pmoles of phosphate incorporated during a 10 min incubation. Controls are performed with appropriate dilutions of dimethylsulfoxide. In a few cases phosphorylation of the substrate is assessed by autoradiography after SDS–PAGE. GSK–3α/β is purified from porcine brain by affinity chromatography on immobilized axin. It is assayed, following a 1/100 dilution in 1 mg BSA/mL 10 mM DTT, with 5 μL 40 μM GS–1 peptide, a specific GSK–3 substrate, in buffer A, in the presence of 15 μM [γ–32P] ATP (3,000 Ci/mmol; 1 mCi/mL) in a final volume of 30 μL. After 30 min incubation at 30°C, 25 μL aliquots ofsupernatant are spotted onto 2.5×3 cm pieces of Whatman P81 phosphocellulose paper, and 20 seconds later, the filters are washed five times (for at least 5 min each time) in a solution of 10 mL phosphoric acid/liter of water. The wet filters are counted in the presence of 1 mL ACS scintillation fluid.Cell Assay:[1]COS1, Hepa (wild–type, CEM/LM AhR deficient and ELB1 ARNT deficient), or SH–SY5Y cells are grown in 6 cm culture dishes in Dulbecco's Modified Medium (DMEM) containing 10% fetal bovine serum. For treatment, IO (5 μM), BIO (5 or 10 μM), MeBIO (5 or 50 μM), LiCl (20 or 40 mM), or mock solution (DMSO, 0.5% final concentration) is added to medium when cell density reaches appr 70% confluence. After 12 (SH–SY5Y) or 24 hours, the cells, while still in plate, are lysed with lysis buffer (1% SDS, 1 mM sodium orthovanadate, 10 mM Tris [pH 7.4]). The lysate is passed several times through a 26G needle, centrifuged at 10,000× g for 5 min, and adjusted to equal protein concentration. About 8 μg of each sample is loaded for immunoblotting. Enhanced chemiluminescence is used for detection. The following primary antibodies are used: mouse anti–β–catenin CT, mouse anti–phospho–β–catenin, mouse anti–GSK–3 β, mouse anti–GSK–3 phosphoTyr216, rabbit anti–AhR (Aryl hydrocarbon receptor), and rabbit anti–actin.Product Name:BIO Cat. No.:HY-10580CAS No.:667463-62-9Molecular Formula:C 16H 10BrN 3O 2Molecular Weight:356.17Target:GSK–3; GSK–3; CDK Pathway:Stem Cell/Wnt; PI3K/Akt/mTOR; Cell Cycle/DNA Damage Solubility:DMSO: ≥ 23 mg/mLAnimal Administration: BIO is freshly prepared in 30% Solutol as 10 mg/mL.[4]BALB/c mice (at 6–8 weeks old) and immunodeficient NOD/SCID/IL2Rgamma null (NSG) mice (female at 6–8 weeks old) are used in the assay. A2058 human melanoma cells at 5×106 cells in serum free medium are inoculated subcutaneously into the dorsal area of NSG mice to create xenograft model. When tumors become palpable, 6BIO or vehicle control is administered via oral gavage once daily at 50 mg/kg body weight. Tumor growth is monitored every other day. Tumor volumes are measured every 3 to 4 days. Tumor volumes are calculated using the formula: 0.5 ×(larger diameter) × (small diameter)2.References:[1]. Meijer L, et al. GSK–3–selective inhibitors derived from Tyrian purple indirubins. Chem Biol. 2003 Dec;10(12):1255–66.[2]. Sato N, et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK–3–specific inhibitor. Nat Med. 2004 Jan;10(1):55–63. Epub 2003 Dec 21.[3]. Tseng AS, et al. The GSK–3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem Biol. 2006 Sep;13(9):957–63.[4]. Liu L1, et al. 6–Bromoindirubin–3'–oxime inhibits JAK/STAT3 signaling and induces apoptosis of human melanoma cells. Cancer Res. 2011 Jun 1;71(11):3972–9.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
Febuxostat_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Jul.-04-2017Print Date:Jul.-04-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :FebuxostatCatalog No. :HY-14268CAS No. :144060-53-71.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4), H302Acute aquatic toxicity (Category 1), H400Chronic aquatic toxicity (Category 1), H4102.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if swallowed.H410 Very toxic to aquatic life with long lasting effects.Precautionary statement(s)P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P273 Avoid release to the environment.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor/ physician if you feel unwell.P330 Rinse mouth.P391 Collect spillage.P501 Dispose of contents/ container to an approved waste disposal plant.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:TEI 6720; TMX 67Formula:C16H16N2O3SMolecular Weight:316.37CAS No. :144060-53-74. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGUN number: 3077Class: 9Packing group: IIIEMS-No: F-A, S-FProper shipping name: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S.Marine pollutant: Marine pollutantIATAUN number: 3077Class: 9Packing group: IIIProper shipping name: Environmentally hazardous substance, solid, n.o.s.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
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Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
FMK is a an irreversible RSK2 kinase inhibitor, that covalently modifies the C–terminal kinase domain of RSK.
In Vitro: Pretreatment of ARVMs with 3 μM fmk attenuates the increase in Ser386 phosphorylation, but it has no inhibitory effect on the increase in Thr577 phosphorylation [1]. FMK inhibits relatively few protein kinases in the panel, although it does inhibit protein tyrosine kinases, such as Src, Lck, Yes and Eph–A2, as well as S6K1. FMK will not inhibit RSK if the N–terminal kinase domain are activated by a mechanism that is independent of the C–terminal domain [2]. Fmk potently inactivates the CTD auto–kinase activity of RSK1 and RSK2 with high specificity in mammalian cells. Targeting RSK2 by a specific small molecule RSK inhibitor fmk attenuates FGFR3–induced cytokine–independent growth in Ba/F3 cells. FMK inhibits cytokine–independent proliferation of Ba/F3 cells conferred by FGFR3[3].
PROTOCOL (Extracted from published papers and Only for reference)
Kinase Assay:[3]The S6 peptide kinase assay is carried out according to the manufacturer’s protocol using RSK2 immunoprecipitates.To determine the ability of FGFR3 to phosphorylate RSK2, 500 ng of purified recombinant RSK2 variants are incubated with 500 ng of recombinant active FGFR3 in 10 mM HEPES (pH 7.5), 150 mM NaCl, 1 mM DTT, 0.01% Trixton–X–100, 10 mM MnCl 2, and 200 μM ATP for 30 min at 30°C. Phosphorylation of Y529 RSK2 is detected by specific phospho–antibody. To determine kinase activity of RSK2CTD variants, purified recombinant RSK2 CTD proteins (500 nM) are incubated with 500 nM of active ERK in 20 mM HEPES [pH 8.0],10 mM MgCl 2, 2 mM tris–(2–carboxyethyl)–phosphine (TCEP), and 200 μM ATP for 1 hr at 30°C. Kinase reactions are initiated by the addition of 5 μCi of [γ–32P] ATP and 100 μM peptide substrate (CTD–tide), followed by incubation for 20 min at room temperature. Kinase activity is determined using the standard disk phospho–cellulose assay.
Cell Assay:[3]RSK2 expressing Ba/F3 cell lines are generated by retroviral transduction as described by using Ba/F3 cells stably expressing FGFR3 TDII with pMSCV–puro plasmids encoding myc–tagged RSK2 variants, followed by antibiotic selection. For cell viability assays, 1×105 Ba/F3 cells stably expressing FGFR3 are cultured in 24–well plates with media containing
increasing concentrations of FMK, acidic FGF (10 nM), and heparin (30 μg/mL) in the absence of IL–3. The relative cell viability
at each experimental time point is determined by using the Celltiter96AQ ueous One solution proliferation kit.References:
[1]. Cuello F, et al. Evidence for direct regulation of myocardial Na+/H+ exchanger isoform 1 phosphorylation and activity by 90–kDa ribosomal S6 kinase (RSK): effects of the novel and specific RSK inhibitor fmk on responses to alpha1–adrenergic stimulation.
[2]. Bain J, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297–315.
[3]. Kang S, et al. FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell. 2007 Sep;12(3):187–9.
Product Name:
FMK Cat. No.:
HY-52101A CAS No.:
821794-92-7Molecular Formula:
C 18H 19FN 4O 2Molecular Weight:
342.37Target:
Ribosomal S6 Kinase (RSK)Pathway:
MAPK/ERK Pathway Solubility:
10 mM in DMSO
Caution: Product has not been fully validated for medical applications. For research use only.
Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@
Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。