Voruciclib is a pan-inhibitor of cyclin-dependent kinases (CDKs; Kis = 0.626-9.1 nM).1 It is selective for CDKs over male germ cell associated kinase (MAK) and intestinal cell kinase (ICK; Kis = 259 and 481 nM, respectively), in a panel of 48 kinases. Voruciclib decreases myeloid cell leukemia-1 (Mcl-1) levels and increases cleaved poly(ADP-ribose) polymerase (PARP) levels in six diffuse large B-cell lymphoma (DLBCL) cell lines when used at concentrations ranging from 0.5 to 5 μM. It reduces tumor growth by 56.3% in a Ri-1 mouse xenograft model when administered at a dose of 200 mg/kg.
|1. Dey, J., Deckwerth, T.L., Kerwin, W.S., et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk diffuse large B-cell lymphoma to BCL2 inhibition. Sci. Rep. 7(1), 18007 (2017).