AP23464

845895-51-4

Apoptosis, Others, c-Kit

Apoptosis, Others, Tyrosine Kinase/Adaptors

AP23464 is a potent adenosine 5'-triphosphate (ATP) -based inhibitor of Src and Abl kinases, displays antiproliferative activity against a human CML cell line and Bcr-Abl-transduced Ba/F3 cells (IC (50) = 14 nM. AP23464 ablates Bcr-Abl tyrosine phosphorylation, blocks cell cycle progression, and promotes apoptosis of Bcr-Abl-expressing cells. Biochemical assays with purified glutathione S transferase (GST) -Abl kinase domain confirmed that AP23464 directly inhibits Abl activity. Importantly, the low nanomolar cellular and biochemical inhibitory properties of AP23464 extend to frequently observed imatinib mesylate-resistant Bcr-Abl mutants, including nucleotide binding P-loop mutants Q252H, Y253F, E255K, C-terminal loop mutant M351T, and activation loop mutant H396P. AP23464 was ineffective against mutant T315I, an imatinib mesylate contact residue. The potency of AP23464 against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warr......

N(C1=C2C(N(CCC3=CC(O)=CC=C3)C=N2)=NC(=N1)C4CCCC4)C5=CC=C(P(C)(C)=O)C=C5

C26H30N5O2P

475.52

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