CCT137690 is a potent inhibitor of Aurora kinases (IC50s = 15, 25 and 19 nM for Aurora A, B, and C, respectively). It also inhibits the receptor tyrosine kinase FLT3 as well as the constitutively active form of FLT3 bearing internal-tandem duplications (FLT3-ITD; IC50s = 1.2 and 4.9 nM, respectively). CCT137690 is orally bioavailable, inhibiting the growth of SW620 colon carcinoma xenografts in mice without inducing body weight loss. It blocks signaling through Aurora kinases in MYCN-amplified neuroblastoma cells, suppressing N-Myc expression and preventing proliferation. It inhibits growth of FLT3-ITD cells harboring a D835Y mutation, which confers resistance to other FLT3 inhibitors. CCT137690 also sensitizes colorectal carcinoma cells to radiotherapy.
