CCT137690

CCT137690 is a potent inhibitor of Aurora kinases (IC₅₀s = 15, 25 and 19 nM for Aurora A, B, and C, respectively).¹ 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).¹ CCT137690 is orally bioavailable, inhibiting the growth of SW620 colon carcinoma xenografts in mice without inducing body weight loss.¹ It blocks signaling through Aurora kinases in MYCN-amplified neuroblastoma cells, suppressing N-Myc expression and preventing proliferation.² It inhibits growth of FLT3-ITD cells harboring a D835Y mutation, which confers resistance to other FLT3 inhibitors.³ CCT137690 also sensitizes colorectal carcinoma cells to radiotherapy.⁴

WARNING This product is not for human or veterinary use.

1. Bavetsias, V., Crumpler, S., Sun, C., et al. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: Identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J. Med. Chem. 55(20), 8721-8734 (2012).

2. Faisal, A., Vaughan, L., Bavetsias, V., et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol. Cancer Ther. 10(11), 2115-2123 (2011).

3. Moore, A.S., Faisal, A., Gonzalez de Castro, D., et al. Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia 26(7), 1462-1470 (2012).

4. Wu, X., Liu, W., Cao, Q., et al. Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy. J. Exp. Clin. Cancer Res. 33, 1-9 (2014).