Aurora kinase and FMS-like Tyrosine Receptor 3 (FLT3) was found to associate with various cancers, including breast cancers, colorectal cancers, AML and so on. There are several Aurora kinase inhibitors and FLT3 inhibitors was developed and under clinical investigation. And no Aurora kinase inhibitors or FLT3 inhibitors currently approved for the treatment of cancers still.[p]We synthesized more than 1000 compounds mainly targeted at Aurora kinase. BPR1K871, a novel, potent, small-molecule inhibitor of multiple kinase showed potent in vitro activities for Aurora kinase A (IC50: 50 nM), FLT-3 (IC50: 29 nM) and at least other 17 kinases with low IC50 activities (nano molar range). In cell-based assay, BPR1K871also demonstrated its excellent anticancer activities (HCT116: 117 nM, MOLM-13: 2 nM, MIA Paca-2: 9 nM, Colo205: 33 nM). In the MOLM-13 xenograft animal studies, BPR1K871 suppressed tumor growth up to 98% at 3 mg/kg once a day for 10-day treatment by IV administration. The body weight loss is less than 5% during the dosing period. This non-clinical profile of BPR1K871 supports the further pre-clinical development.
Date:
2012-03-25
Relation:
Abstracts of Papers - American Chemical Society. 2012 Mar 25;243:Article number 48-MEDI.
