CDKs (Cyclin-dependent kinases) are serine-threonine kinases first discovered for their role in regulating the cell cycle. They play roles in regulating transcription, mRNA processing, and the differentiation of nerve cells. To date, there are approximately 20 cyclin-dependent kinases (CDK1-20). CDK1, 4, and 5 play a role in the cell cycle, and CDKs 7, 8, 9, and 11 can regulate transcription. CDK levels remain relatively constant throughout the cell cycle, and most regulation occurs post-translationally. Dinaciclib (SCH 727965) is a potent inhibitor of CDK, with IC50s of 1 nM, 1 nM, 3 nM, and 4 nM for CDK2, CDK5, CDK1, and CDK9, respectively.

Dinaciclib (SCH 727965) is a potent CDK inhibitor for pancreatic cancer research.

SCH 727965 is a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with an IC50 of 4 nM. Firstly, it (100 nM) inhibits phosphorylation of the retinoblastoma (Rb) tumor suppressor protein and induces accumulation of the p85 PARP caspase cleavage product. Importantly, these results are consistent with studies of Dinaciclib in other cancer cell lines. In soft agar assays, 5 to 10 nM of Dinaciclib significantly reduces colony formation and anchorage-independent growth of MIAPaCa-2 cells. Moreover, in vitro cell migration of Pa20C and MIAPaCa-2 cells is significantly reduced by Dinaciclib concentrations starting from 2-5 nM.

In addition, Dinaciclib (8, 16, 32, and 48 mg/kg, i.p.) results in tumor inhibition by 70%, 70%, 89%, and 96%, respectively. Besides, it is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. Dinaciclib has a short plasma half-life in mice. Moreover, treatment with Dinaciclib given twice weekly i.p. doses of 40 mg/kg for 4 weeks causes significant tumor growth inhibition (TGI) in 10/10 (100%) of low-passage subcutaneous pancreatic xenografts tested.

In conclusion, Dinaciclib (SCH 727965) is a potent and selective CDK inhibitor for cancer research.


[1] David Parry, et al. Mol Cancer Ther. 2010 Aug;9(8):2344-53. 

[2] Georg Feldmann, et al. Cancer Biol Ther. 2011 Oct 1;12(7):598-609.