title: Seliciclib, a cell-cycle modulator that acts through the inhibition of cyclin-dependent kinases.
abstract: Seliciclib is an inhibitor of cyclin-dependent kinases 2, 7 and 9. Its primary mechanism of action is the inhibition of transcription, resulting in the selective downregulation of rapidly cycling mRNA transcripts, including Mcl-1 and cyclin D1. It possesses antitumour activity as a single agent and also synergises with a wide range of cytotoxic and targeted drugs. Seliciclib has high oral bioavailability and is in clinical development in a capsule formulation. The clinical dose has been determined in Phase I clinical trials for schedules of 3 - 10 consecutive days per cycle of 2 or 3 weeks duration. Its major clinical toxicities include nausea, vomiting, asthenia, hypokalaemia, elevation of creatinine levels and liver function tests, which are reversible after cessation of dosing. Seliciclib is non-myelosuppressive and does not cause intestinal toxicity. Phase II trials have commenced in non-small cell lung cancer and will be initiated shortly in nasopharyngeal carcinoma.
authors.affiliation: Pharmacometrics Ltd, 51 North Road, Whittlesford, Cambridge CB22 4NZ, UK +44 1382 206062 ; +44 1382 206067 ; rjackson1943@aol.com.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Jackson
authors.forename: Anna L
authors.initials: AL
authors.lastname: Barnett
authors.forename: Steven J
authors.initials: SJ
authors.lastname: McClue
authors.forename: Simon R
authors.initials: SR
authors.lastname: Green