Seliciclib in malignancies

Ibrahim T. Aldoss, Tsewang Tashi, Apar Kishor Ganti

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The majsor adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Original languageEnglish (US)
Pages (from-to)1957-1965
Number of pages9
JournalExpert Opinion on Investigational Drugs
Volume18
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Cancer
  • Cell cycle
  • Cyclin-dependent kinase inhibitor
  • Roscovitine
  • Seliciclib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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