Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

Abstract

Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of the published in vitro and in vivo work supporting the development as an anti-cancer agent, from in vitro experiments to animal model studies ending with a summary of the clinical trial results and trials underway is presented. In addition some potential non-oncology applications are explored and the potential mode of action of Seliciclib in these areas is described. Finally the authors argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division.

Human pluripotent stem-cell-derived cardiomyocytes in cardiovascular drug discovery and development

“…The use of Roscovitine, a drug known to inhibit CDK-related activity in tumour cells, has demonstrated positive results in the prevention of cardiac hypertrophy [24][25][26][27]. The results suggest that cardiac hypertrophy is accompanied by activation of CDK9, and that target based inhibitors of the kinase pathway may be suitable molecular targets for therapeutic intervention in HCM.…”