CDK inhibitors in clinical development for the treatment of cancer

Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma

“…Based on in vitro kinase assays, it has specificity against CDKs, acting on CDK2/cyclin A, CDK2/cyclin E, CDK7/ cyclin H, and CDK9/cyclinT1. [17][18][19][20][21][22][23] Its activity against several CDKs may be one of the mechanisms by which it preferentially results in apoptosis, as opposed to growth arrest, of cancer cells. Here we study the in vitro effects and molecular mechanisms of action of seliciclib against MM cells alone and bound to BMSCs.…”

Cell cycle molecules and vertebrate neuron death: E2F at the hub

“…37 Although supportive, the drawback of such studies is that, as with many small molecules, there is the issue of flavopridol's specificity that appears to include at least several additional targets that might also affect neuron survival. 74 On the positive side, flavopiridol, which is currently in clinical trials as an anticancer agent, 69,75 appears to be remarkably effective in promoting neuron survival, is well tolerated in patients and thus it or a related compound may prove to be clinically useful as a neuroprotective agent.…”

“…One example is flavopiridol that is currently in clinical trials for cancer. 74,75,128 Although the exact mechanism by which this cdk inhibitor protects neurons is unclear, it does appear to represent a powerful starting point to design drugs that block the E2F pathway and that may repress catastrophic neuron death. Many additional agents have been developed that affect the E2F pathway and it would seem to be of high priority to assess these and derivatives for neuroprotective activity.…”

Tumor suppressor pRb2/p130 gene and its derived product Spa310 spacer domain as perspective candidates for cancer therapy

“…In this respect, many pharmacological cdks inhibitors with potent antitumor activity were produced and characterized. However, only a restrict number of these drugs are currently under preclinical and clinical evaluation (Fischer and Giannella-Borradori, 2003). The field of cancer research is now focusing its efforts in developing novel means to target cdk2, which is considered the prototypic cell cycle kinase, because of its crucial role in regulating cell cycle progression in mammalian cells (Koff et al, 1992;Ohtsubo et al, 1995).…”