A-3465 Alvocidib, Free Base, >99%

Synonyms : [CPB] [DB03496] [Flavo] [Flavopiridol] [HL-275] [HMR-1275] [L86-8275] [LS-39494] [MDL 107,826A]

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  • M.W. 401.84
  • C21H20ClNO5
  • [146426-40-6]
  • M.I. 14: 4094

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A.

  • Alvocidib, also known as flavopiridol or HMR-1275, is a cyclin-dependent kinase (CDK) inhibitor.
  • Alvocidib is a broad-spectrum inhibitor of CDKs and targets their ATP binding sites. It promotes cell cycle arrest and apoptosis, induces differentiation, blocks transcription elongation, and inhibits angiogenesis. Senderowicz, A.M. "Small-molecule cyclin-dependent kinase modulators." Oncogene 22: 6609-6620 (2003).
  • Administration of flavopiridol to older (>70 years) chronic lymphocytic leukemia patients is feasible, tolerable, and has comparable efficacy to that in younger patients (<70 years). Stephens, D.M., et al. "Flavopiridol treatment of patients aged 70 or older with refractory or relapsed chronic lymphocytic leukemia is a feasible and active therapeutic approach." Haematologica 97: 423-427 (2012).
  • Preclinical studies have shown that alvocidib induces apoptosis in both normal and malignant cells, particularly those of hematopoietic origin. Arguello, F., et al. "Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts." Blood 91: 2482-2490 (1998).
  • Alvocidib potentiates paclitaxel-induced apoptosis in the human gastric and breast cancer cell lines MKN-74 and MCF-7. Motwani, M., et al. "Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells." Clin. Cancer Res. 5: 1876-1883 (1999).
  • Alvocidib (100-200 nM) potentiates phorbol 12-myristate 13-acetate (PMA, 10 nM)-induced apoptosis in human myeloid leukemia cells U937 and HL-60. Cartee, L., et al. "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: 1313-1321 (2002).
  • In early clinical trials, alvocidib demonstrated limited activity in patients with gastric carcinoma and lung cancer. Schwartz, G.K., et al. "Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma." J. Clin. Oncol. 19: 1985-1992 (2001). Shapiro, G.I., et al. "A Phase II Trial of the Cyclin-dependent Kinase Inhibitor Flavopiridol in Patients with Previously Untreated Stage IV Non-Small Cell Lung Cancer." Clin. Cancer Res. 7: 1590-1599 (2001).
  • In vitro, alvocidib inhibited proliferation of human and mouse synovial fibroblasts. In vivo, treatment with alvocidib suppressed synovial hyperplasia and joint destruction in mice with collagen-induced arthritis. Sekine, C., et al. "Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors." J. Immunol. 180: 1954-1961 (2008).
  • Alvocidib has potent antiviral activity in vitro againest HIV-1 and HSV-1. Schang, L.M. "Effects of pharmacological cyclin-dependent kinase inhibitors on viral transcription and replication." Biochim. Biophys. Acta. 1697: 197-209 (2004).
  • Related CAS numbers: 131740-09-5 for the hydrochloride salt.
  • Another CAS number previously assigned to alvocidib free base, namely 358739-39-6, has been deleted by CAS and is no longer in use.
  • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
  • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
  • Not available in some countries; not available to some institutions; not available for some uses.
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