FLAVOPIRIDOL HYDROCHLORIDE

Description

Flavopiridol is an orally bioavailable inhibitor of cyclin dependent kinases (IC₅₀s = ~100, ~100, ~100, and 300 nM for Cdk1, Cdk2, Cdk4, and Cdk7, respectively). It also inhibits TEFb, a complex composed of Cdk9 and cyclin T1, with a K_i value of 3 nM. Flavopiridol inhibits transcription of a CMV promoter in HeLa nuclear extract (IC₅₀ = 34 nM), Tat-stimulated transcription of an HIV-1 promotor (IC₅₀ = 7 nM), and HIV-1 replication in HEK239T cells (IC₅₀ = <10 nM). In vivo, flavopiridol (5 mg/kg, i.p.) induces apoptosis and cyclin D1 depletion and delays tumor growth in an HN-12 head and neck carcinoma mouse xenograft model. It also suppresses synovial hyperplasia and joint destruction in a mouse model of collagen-induced arthritis.

Chemical Properties

Yellow Powder

Uses

Flavopiridol hydrochloride hydrate has been used:

• as a cyclin-dependent kinase 9 (CDK9) inhibitor to study its effects on histone H3 methylation at lysine 36 (H3K36) and deactivation of transcription in porcine fetal fibroblasts
• as an RNA polymerase inhibitor to study its effects on hepatic cells
• as RNA transcription inhibitor to study its effects on euchromatin coarsening in zebrafish embryo

Uses

An inhibitor of cyclin-dependent kinases; the (-)-cis form induces apoptosis in certain tumor cells.

Definition

ChEBI: A hydrochloride salt resulting from the formal reaction of equimolar amounts of alvocidib and hydrogen chloride. A cyclin-dependent kinase 9 (CDK9) inhibitor, it has been studied for the treatment of acute myeloid leukaemia, arthritis and atherosclerotic p aque formation.

Biochem/physiol Actions

Flavopiridol?is a semi-synthetic flavone obtained from Dysoxylum binectariferum that acts as an anti-tumor agent against several cancers. It also shows anti-cancer properties due to which it has been studied in the treatment of acute myeloid leukemia (AML).

storage

Store at +4°C

References

1) Kaur?et al. (1992),?Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275;? J. Natl. Cancer Inst.,?84?1736 2) Cartee?et al. (2002),?Synergistic induction of apoptosis in human myeloid leukemia cells by phorbol 12-myristate 13-acetate and flavopiridol proceeds via activation of both the intrinsic and tumor necrosis factor-mediated extrinsic cell death pathways;? Mol. Pharmacol.,?61?1313 3) Ambrosini?et al. (2008),?The cyclin-dependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase I poisons by suppressing Rad51 expression in a p53-dependent manner;? Cancer Res.?68?2312 4) Schang?et al. (2004),?Effects of pharmacological cyclin-dependent kinase inhibitors on viral transcription and replication;? Biochim. Biophys. Acta,?1697?197