Early development of cyclin dependent kinase modulators

The protein kinase family presents remarkable opportunities for drug discov ery and development targeting mainly to the ATP binding cleft. Cyclin-depen dent kinases CDKs control the cell division in by controlling its sub phase s. The regulation of CDKs is altered in a number of tumor types, and theref ore CDKs are a particularly attractive target group of kinases with referen ce to proliferative disorders including cancer, but also extending to graft stenosis, and autoimmune disorders. Screening of chemical modulators of CD Ks that modulate aberrant CDK activity might be beneficial for cancer thera py by directly inhibiting kinase activity, or influencing cell cycle "check point" function, which is mediated through effects of exogenous cellular re gulators of CDK activity. In this regard small molecule modulators such as flavopiridol and UCN-01 are in early clinical trials. Other more selective modulators of CDK function are being actively sought, and initial results w ith flavopiridol analogs, indirubins, paullones, and purine-based inhibitor s will be considered.