Biomedicinal Chemistry
The work of the biomedicinal chemists is focused on the discovery of small molecule compounds (i.e. MW < 500 g/mol) targeted against the basic molecular mechanisms of the pathogenesis of cancer, especially oncogenic protein kinases. The strategy is to study structure-activity relationships of active compounds and develop selective drugs that either block proliferation or induce apoptosis of cancer cells.
In recent years, as well as 2,6,9-trisubstituted purines, a number of other pharmacological CDK inhibitors with a wide variety of
cellular impacts has been developed and synthesized in our laboratory, including pyrazolo[4,3-d]pyrimidines
and 8-azapurines. The syntheses of the designed derivatives are carried out by the methods of classical organic synthesis.
Effective compounds are subsequently prepared in a radioactive form (labelled mainly with 3H-isotope) for pharmacological studies.
Recent developments in our laboratory have led to the identification of selective inhibitors of cyclin-dependent kinases 1, 2, 7 and 9 with promising anticancer activity. One of the derivatives, roscovitine (CYC202 or Seliciclib), is now undergoing Phase II clinical trials against several cancers in Great Britain, Germany and France.