Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance.
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.
CMCBR, SIMBIOS, School of Science, Engineering and Technology, Abertay University, Dundee DD1 1HG, Scotland, UK.
Hilal S
HS
Khalil
Department of Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia, Bulgaria.
Vanio
V
Mitev
Department of Chemistry and Biochemistry, Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
Tatyana
T
Vlaykova
CMCBR, SIMBIOS, School of Science, Engineering and Technology, Abertay University, Dundee DD1 1HG, Scotland, UK.
Laura
L
Cavicchi
CMCBR, SIMBIOS, School of Science, Engineering and Technology, Abertay University, Dundee DD1 1HG, Scotland, UK. Electronic address: n.zhelev@abertay.ac.uk.
Nikolai
N
Zhelev
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D058492:Drug Repositioning / Q000379:methods*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D000077546:Roscovitine; D049490:Systems Biology / Q000379:methods*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases
CDK; Seliciclib; Systems biology