131740-09-5 Usage
Description
Flavopiridol hydrochloride is an orally bioavailable inhibitor of cyclin-dependent kinases (CDKs), with IC50s of approximately 100 nM for Cdk1, Cdk2, Cdk4, and 300 nM for Cdk7. It also inhibits the TEFb complex, composed of Cdk9 and cyclin T1, with a Ki value of 3 nM. Flavopiridol hydrochloride is a yellow powder and has been studied for its potential therapeutic applications in various diseases.
Uses
Used in Pharmaceutical Industry:
Flavopiridol hydrochloride is used as an inhibitor of cyclin-dependent kinases for its potential therapeutic effects in treating various types of cancer. The (-)-cis form of flavopiridol hydrochloride induces apoptosis in certain tumor cells, making it a promising candidate for cancer treatment.
Used in Research Applications:
1. Flavopiridol hydrochloride is 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.
2. It is used as an RNA polymerase inhibitor to study its effects on hepatic cells.
3. Flavopiridol hydrochloride is used as an RNA transcription inhibitor to study its effects on euchromatin coarsening in zebrafish embryos.
In vivo studies have shown that flavopiridol hydrochloride (5 mg/kg, i.p.) induces apoptosis and cyclin D1 depletion, delays tumor growth in an HN-12 head and neck carcinoma mouse xenograft model, and suppresses synovial hyperplasia and joint destruction in a mouse model of collagen-induced arthritis. It has also been studied for the treatment of acute myeloid leukemia, arthritis, and atherosclerotic plaque 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).
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
Check Digit Verification of cas no
The CAS Registry Mumber 131740-09-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,1,7,4 and 0 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 131740-09:
(8*1)+(7*3)+(6*1)+(5*7)+(4*4)+(3*0)+(2*0)+(1*9)=95
95 % 10 = 5
So 131740-09-5 is a valid CAS Registry Number.
InChI:InChI=1/C21H20ClNO5.ClH/c1-23-7-6-12(17(27)10-23)19-14(24)8-15(25)20-16(26)9-18(28-21(19)20)11-4-2-3-5-13(11)22;/h2-5,8-9,12,17,24-25,27H,6-7,10H2,1H3;1H/t12-,17+;/m0./s1
131740-09-5Relevant articles and documents
Application of modified flavone closure for the preparation of racemic L86-8275
Tabaka, A. Christine,Murthi, Krishna K.,Pal, Kollol,Teleha, Christopher A.
, p. 256 - 259 (1999)
The laboratory preparation of racemic L86-8275 (1a) and the salt (1b) is described in 7% overall yield. Our method eliminated a number of chromatography steps from the patent procedure and improved the flavone-forming reaction by employing a stepwise mechanism. Solvent-free conditions for the demethylation step are also described.