Flavopiridol (Alvocidib)

Alvocidib is a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity. Check for active clinical trials or closed clinical trials using this agent.

Product information

CAS Number: 146426-40-6

Molecular Weight: 401.84

Formula: C21H20ClNO5

Synonym:

L 86-8275

L-868275

L 868275

L868275

HMR 1274

HMR-1274

HMR1274

Flavoperidol

Alvocidib

Related CAS Number:

131740-09-5 (Alvocidib HCl)

Chemical Name: 2-(2-chlorophenyl)-5, 7-dihydroxy-8-((3R, 4S)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one

Smiles: CN1C[C@H](O)[C@@H](CC1)C1=C2OC(=CC(=O)C2=C(O)C=C1O)C1=CC=CC=C1Cl

InChiKey: BIIVYFLTOXDAOV-PXAZEXFGSA-N

InChi: InChI=1S/C21H20ClNO5/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/t12-,17+/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 15 mg/mL(37.32 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Flavopiridol displays less activity against unrelated kinases such as MAP, PAK, PKC, and EGFR with IC50 of >14 μM. Flavopiridol significantly inhibits the colony growth of HCT116, A2780, PC3, and Mia PaCa-2 cells with IC50 of 13 nM, 15 nM, 10 nM and 36 nM, respecitively. Flavopiridol also potently inhibits the activity of Glycogen synthase kinase-3 (GSK-3) with an IC50 of 280 nm. Compared with other CDKs, Flavopiridol inhibits the activity of CDK7 less potently with IC50 of 875 nM. Flavopiridol (0.5 μM) inhibits both pSer807/811 Rb and pThr199 NPM, whereas mild changes are observed at pThr821 Rb. Flavopiridol also decreases the overall RNA polymerase II level, as well as the phosphorylation of RNA polymerase II on the CTD repeats at Ser2 Ser5. As a broad spectrum CDK inhibitor, Flavopiridol can inhibit cell cycle progression in either G1 or G2. Flavopiridol (0.3 μM) induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. Flavopiridol exhibits potent cytotoxicity against a wide variety of tumor cell lines with IC50 values ranging form 16 nM for LNCAP to 130 nM for K562.

In Vivo:

Administration of Flavopiridol at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, resulting in %T/C value of 110, and active against the human A2780 ovarian carcinoma implanted sc in nude mice, producing 1.5 log cell kill (LCK). Flavopiridol treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. In the p21-intact Hct116 xenografts in nude mice, administration of CPT-11 (100 mg/kg) followed by Flavopiridol (3 mg/kg) 7 and 16 hours later significantly inhibits tumor regression by 86% and 82%, respectively, displaying >2 fold inhibition compared with CPT-11 alone by 40 %. The combination produces ~30% complete response rate (CR) in contrast to CPT-11 alone where no CR is found.

References:

1. Montagnoli A, et al. Nat Chem Biol, 2008, 4(6), 357-365.
2. Lu H, et al. J Med Chem, 2005, 48(3), 737-743.
3. Kim KS, et al. J Med Chem, 2000, 43(22), 4126-4134.

Products are for research use only. Not for human use.