635702-64-6

溶解度:DMSO

储存条件:at -20C 2 years

生物活性

AP24534 is a novel potent, orally available small molecule multitargeted kinase inhibitor with IC50 of 0.37, 2, 1.5, 2.2, 1.1, 1and 0.24 nM for native pan-BCR-ABL, mutated form, VEGFR2, FGFR1, PDGFRα, mutant FLT3 phosphorylation and LYN.
It potently inhibited other clinically important ABL kinase domain mutants with IC50 from 0.30 to 0.44 nM and inhibited SRC with an IC50 of 5.4 nM. It inhibits the proliferation of mutant FLT3-positive cells with an IC50 of 13 nM and that inhibits mutant FLT3 phosphorylation with an IC50 of 1 nM and the proliferation of BCR-ABL1 T315I-positive Ba/F3 cells with an IC50 of 8 nM. It inhibited all tested BCR-ABL mutants with low nM IC50s in cellular and biochemical assays, suppressed BCR-ABL(T315I)-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. AP24534 is used for treatment of CML. It did not inhibit Aurora kinase family members, nor did it inhibit insulin receptor or cyclin-
dependent kinase 2 (CDK2)/Cyclin E (IC50 > 1000-fold relative to native ABL.

参考文献

[1] O'Hare T et al. Cancer Cell. 2009 Nov 6;16(5):401-12.

[2] Huang WS et al. J Med Chem. 2010 Jun 24;53(12):4701-19.