Flavopiridol

SKU: orb1685546

Description

Flavopiridol (Alvocidib) is a potent ATP-competitive inhibitor of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6 (IC50 ~40 nM), demonstrating selectivity over CDK7. It has been investigated in preclinical and clinical studies (Phase 1/2) for oncology research, showing activity in both in vitro cell proliferation assays and in vivo tumor models.

Research Area

Cell Biology, Infectious Disease & Virology, Protein Biochemistry

Key Properties

• CAS Number: 146426-40-6
• MW: 401.84
• Purity: 99.99% (May vary between batches)
• Formula: C₂₁H₂₀ClNO₅
• SMILES: CN1CC[C@@H]([C@H](O)C1)c1c(O)cc(O)c2c1oc(cc2=O)-c1ccccc1Cl
• Target: Apoptosis,Autophagy,HIV Protease,CDK
• Solubility: DMSO:34 mg/mL (84.61 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.98 mM);Ethanol:8 mg/mL (19.91 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  MAP:19000 nM|CDK1:40 nM|PKC:14000 nM|CDK6:40 nM|EGFR:22000 nM|CDK2:40 nM|CDK4:40 nM
• 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.
• 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.
• Cell Research:
  Cells are exposed to various concentrations of Flavopiridol for 72 hours at which time the tetrazolium dye, MTS in combination with phenazine methosulfate, is added. After 3 hours, the absorbency is measured at 492 nm, which is proportional to the number of viable cells. The results are expressed as IC50 values. For cell Cycle analysis, cells are fixed in paraformaldehyde and ethanol, washed, resuspended in staining solution of TdT enzyme and FITC-dUTP, washed, stained with PI following RNase treatment, and then analyzed by flow cytometry. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Alvocidib, Apoptosis, Autophagy, CDK6, CDK7, CDK4, CDK, CDK1, CDK2, Cyclin dependent kinase, HIV, HIV Protease, HIVProtease, HMR 1275, HMR1275, HMR-1275, L868275, L-868275, L86-8275, Inhibitor, Human immunodeficiency virus, Flavopiridol, inhibit, NSC 649890 HCl, L 868275

Compound Identifiers

PubChem CID

5287969