AZD8931_Protein Tyrosine Kinase_EGFR-HER2_CAS号848942-61-0说明书_AbMole中国

分子量473.93
溶解性（25°C）
DMSO 40 mg/mL
分子式C H ClFN O Water <1 mg/mL
CAS号848942-61-0Ethanol <1 mg/mL
储存条件3年 -20°C 粉末状
生物活性
AZD8931 (Sapitinib)是一种可逆的，ATP竞争性EGFR， ErbB2和ErbB3抑制剂，IC50分别为4 nM， 3 nM和4 nM，作用于NSCLC细胞比Gefitinib或Lapatinib更有效，作用于ErbB家族比作用于MNK1和Flt选择性强100倍。

AZD8931作用于NSCLC和SCCHN 细胞系的效果不同。

AZD8931高度选择性作用于 PC-9细胞(EGFR 激活突变型),GI50为0.1 nM，而低活性作用于 NCI-1437细胞，GI50 >10 μM。

与lapatinib 或 gefitinib相比，AZD8931作用于 PE/CA-PJ41, PE/CA-PJ49, DOK 和FaDu细胞，更有效作用于p-EGFR, p-erbB2 和 p-erbB3。

实验操作来自于公开的文献，仅供参考
细胞实验
细胞系 a panel of NSCLC and SCCHN cell lines: KYSE-30, OE21, PE/CA-PJ15, PE/CA-PJ34 (clone C12), PE/CA-PJ41 (clone D2), PE/CA-PJ49, DOK, Detroit562, RPMI2650, SCC-4, SCC-9, SCC-25, CAL 27, SW579, FaDu, Hs 840.T, KB, KYSE-450, and HEp-2, HN5; PC-9,
Calu-3, NCI-H2073, NCI-H1623, NCI-H522, NCI-H2085, NCI-H2030, NCI-H1703, NCI-H2291, NCI-H2135, NCI-H1975, NCI-H23, NCI-
H1650, NCI-H1437, NCI-H3255, and NCI-H1666 cell lines
方法cell viability assay. To determine their antiproliferative activity against cell lines grown in vitro, AZD8931, gefitinib, and lapatinib were tested in a panel of NSCLC and SCCHN cell lines. Cells were incubated for 96 h with a suitable range of concentrations of drug to
ensure accurate estimation of the inhibitor concentration required to give 50% growth inhibition (GI50; typically between 0.001-10
μmol/L). Viable cell number was determined by 4 h of incubation with MTS Colorimetric Assay reagent (Promega) and absorbance
measured at 490 nm on a spectrophotometer (Molecular Devices). Each experiment was carried out in triplicate for each drug
concentration and data are presented as geometric means. Sensitivity groupings of GI50 data were <1 μmol/L (classed as sensitive), 1
to 7 μmol/L (classed as intermediate), and >7 μmol/L (classed as resistant).
浓度0~10μM
处理时间96 h
动物实验
动物模型BT474c, Calu-3, LoVo, FaDu and PC-9 xenograft mouse models
配制suspended in a 1% (v/v) solution of polyoxyethylenesorbitan monooleate (Tween 80) in deionized water
剂量 6.25-50 mg/kg twice daily
给药处理oral gavage
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
小鼠大鼠兔豚鼠仓鼠狗
重量 (kg)0.020.15 1.80.40.0810
体表面积 (m)0.0070.0250.150.050.020.5
K系数36128520
动物 A (mg/kg) = 动物 B (mg/kg) × 动物 B的K系数
AZD8931 目录号M1667
化学数据
232553
2
m
m
动物 A 的K 系数
例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K 系数（3），再除以大鼠的K 系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg 。

m m m。