PD 180970

一种Bcr-Abl抑制剂；抑制野生型和突变型Bcr-Abl以及p210亚型（IC50值为5-48nM）；对Bcr-Abl的选择性高于碱性成纤维细胞生长因子受体（bFGFR）和血小板衍生生长因子受体（PDGFR）（IC50值分别为934nM和1430nM），同时抑制Src、Lck、Kit和EGFR（IC50值分别为0.8nM、1nM和1nM）。该化合物在50nM浓度下诱导K562细胞的G1期阻滞和凋亡；抑制MDA-MB-468乳腺癌细胞中STAT3的DNA结合活性及其增殖；抑制对伊马替尼耐药的突变型p210 Bcr-AblY253F Ba/F3细胞的增殖。A Bcr-Abl inhibitor; inhibits wild-type and mutant forms of Bcr-Abl, as well as the p210 isoform (IC50s = 5-48 nM); selective for Bcr-Abl over bFGFR and PDGFR (IC50s = 934 and 1,430 nM, respectively) but also inhibits Src, LCK, KIT, and EGFR (IC50s = 0.8, 1 phase and apoptosis in K562 cells at 50 nM; inhibits constitutive STAT3 DNA-binding activity in and proliferation of MDA-MB-468 breast cancer cells; inhibits proliferation of imatinib-resistant mutant p210 Bcr-AblY253F Ba/F3 cells.分子式C21H15Cl2FN4O分子量429.3CC1=C(F)C=CC(NC2=NC=C(C=C(C3=C(Cl)C=CC=C3Cl)C(N4C)=O)C4=N2)=C1