Seliciclib, a cell-cycle modulator that acts through the inhibition of cyclin-dependent kinases.
Expert Opin Drug Discov
; 3(1): 131-43, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-23480144
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.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article