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Signaling Pathway



(L868275; HMR-1275; Alvocidib)


Flavopiridol Chemical Structure

Flavopiridol competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7.

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Product name: Flavopiridol
Cat. No.: HY-10005

Flavopiridol Data Sheet

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    Purity: 95.85%

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Biological Activity of Flavopiridol

Flavopiridol competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA.
IC50 Value: ~ 40 nM
Target: CDK
in vitro: Flavopiridol induces G1 arrest with inhibition of CDK2 and CDK4 in human breast carcinoma cells in a time and concentration dependent manner. Short time treatment of Flavopiridol (~12 hours) induce apoptosis in hematopoietic cell lines including SUDHL4, SUDHL6 (B-cell lines), Jurkat and MOLT4 (T-cell lines ), and HL60 (myeloid). In the clonogenic assay, Flavopiridol functions as a highly potent cytotoxic compound with a mean IC70 with 8 ng/mL in 23 human tumor models. A recent study shows Flavopiridol treatment induces a substantial AKT-Ser473 phosphorylation in human glioblastoma T98G cell line.
in vivo: After treatment with 7.5 mg/kg Flavopiridol bolus intravenous (IV) or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts undergo complete regressions, and animals remain disease-free several months after one course of Flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days undergo either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay is 73.2%.

Protocol (Extracted from published papers and Only for reference)


Chemical Information

M.Wt 401.84 Storage Please store the product under the recommended conditions in the Certificate of Analysis.
Formula C21H20ClNO5
CAS No 146426-40-6
Solvent & Solubility

DMSO ≥14mg/mL Water <1.2mg/mL Ethanol ≥7.8mg/mL

Preparing Stock Solutions

1 mg 5 mg 10 mg
1 mM 2.4886 mL 12.4428 mL 24.8855 mL
5 mM 0.4977 mL 2.4886 mL 4.9771 mL
10 mM 0.2489 mL 1.2443 mL 2.4886 mL

Clinical Information of Flavopiridol

Product Name Sponsor Only Condition Start Date End Date Phase Last Change Date
Flavopiridol Testis tumor 31-MAY-13 30-SEP-13 Phase 2 06-SEP-13
Ovary tumor 31-MAY-13 30-SEP-13 Phase 2 06-SEP-13
Sidney Kimmel Comprehensive Cancer Center Acute myelogenous leukemia 31-MAY-11 31-JUL-13 Phase 2 14-SEP-13
Eastern Cooperative Oncology Group Acute myelogenous leukemia 31-OCT-08 Phase 2 05-AUG-13
Sidney Kimmel Comprehensive Cancer Center Acute myelogenous leukemia 30-APR-11 Phase 2 17-JUL-13

References on Flavopiridol

[1]. Senderowicz, Adrian M. Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials Investigational New Drugs (1999), 17(3), 313-320

[2]. Mahoney E, Lucas DM, Gupta SV, Wagner AJ, Herman SE, Smith LL, Yeh YY, Andritsos L, Jones JA, Flynn JM, Blum KA, Zhang X, Lehman A, Kong H, Gurcan M, Grever MR, Johnson AJ, Byrd JC.ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.Blood. 2012 Aug 9;120(6):1262-73. Epub 2012 Jun 27.

[3]. Karp JE, Garrett-Mayer EL, Estey EH, Rudek MA, Smith BD, Greer JM, Drye DM, Mackey K, Dorcy KS, Gore SD, Levis MJ, McDevitt MA, Carraway HE, Pratz KW, Gladstone DE, Showell MM, Othus M, Doyle LA, Wright JJ, Pagel JM.Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.Haematologica. 2012 Jun 24.

[4]. Bible KC, Peethambaram PP, Oberg AL, Maples W, Groteluschen DL, Boente M, Burton JK, Gomez Dahl LC, Tibodeau JD, Isham CR, Maguire JL, Shridhar V, Kukla AK, Voll KJ, Mauer MJ, Colevas AD, Wright J, Doyle LA, Erlichman C; the Mayo Phase 2 Consortium (P2C) and North Central Cancer Treatment Group (NCCTG).A Phase 2 Trial of Flavopiridol (Alvocidib) and Cisplatin in Platin-Resistant Ovarian and Primary Peritoneal Carcinoma: MC0261.Gynecol Oncol. 2012 Oct;127(1):55-62. Epub 2012 Jun 1.

[5]. Keskin H, Garriga J, Georlette D, Gra?a X.Complex effects of flavopiridol on the expression of primary response genes.Cell Div. 2012 Mar 29;7:11.

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