Back to products

Browse products

Approved anticancer agents

Anticancer agents in trials

Anticancer agents in preclinical trials

Anticancer molecular libraries

Drug intermediates

Bio-reagents and biochemicals

MedKoo product information:

BIIB021

BIIB021 is An orally active, purine-scaffold, small-molecule inhibitor of heat shock protein 90 (HSP90) with potential antineoplastic activity. HSP90 inhibitor CNF2024 specifically blocks active HSP90, inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; this may result in the inhibition of cellular proliferation in susceptible tumor cell populations. HSP90, a chaperone protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins. BIIB021 that is currently undergoing Phase II testing, may have broader application against tumors with acquired multidrug resistance or tumors located in organs protected by MDR proteins, such as the adrenal glands, brain and testis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer: Memorial Sloan-Kettering Cancer Center

BIIB021 is a novel, fully synthetic inhibitor of Hsp90 that binds competitively with geldanamycin in the ATP-binding pocket of Hsp90. In tumor cells, BIIB021 induced the degradation of Hsp90 client proteins including HER-2, AKT, and Raf-1 and up-regulated expression of the heat shock proteins Hsp70 and Hsp27. BIIB021 treatment resulted in growth inhibition and cell death in cell lines from a variety of tumor types at nanomolar concentrations. Oral administration of BIIB021 led to the degradation of Hsp90 client proteins measured in tumor tissue and resulted in the inhibition of tumor growth in several human tumor xenograft models. Studies to investigate the antitumor effects of BIIB021 showed activity on both daily and intermittent dosing schedules, providing dose schedule flexibility for clinical studies. Assays measuring the HER-2 protein in tumor tissue and the HER-2 extracellular domain in plasma were used to show interdiction of the Hsp90 pathway and utility as potential biomarkers in clinical trials for BIIB021. Together, these data show that BIIB021 is a promising new oral inhibitor of Hsp90 with antitumor activity in preclinical models. (source: Mol Cancer Ther. 2009 Apr;8(4):921-9.).

1: Xu L, Woodward C, Khan S, Prakash C. In Vitro Metabolism of 6-Chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine (BIIB021), an Inhibitor of HSP90, in Liver Microsomes and Hepatocytes of Rats, Dogs, and Humans and Recombinant Human Cytochrome P450 Isoforms. Drug Metab Dispos. 2012 Jan 4. [Epub ahead of print] PubMed PMID: 22217465.

2: Zhang H, Neely L, Lundgren K, Yang YC, Lough R, Timple N, Burrows F. BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance. Int J Cancer. 2010 Mar 1;126(5):1226-34. PubMed PMID: 19676042.

3: Böll B, Eltaib F, Reiners KS, von Tresckow B, Tawadros S, Simhadri VR, Burrows FJ, Lundgren K, Hansen HP, Engert A, von Strandmann EP. Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity. Clin Cancer Res. 2009 Aug 15;15(16):5108-16. Epub 2009 Aug 11. PubMed PMID: 19671844.

4: Yin X, Zhang H, Lundgren K, Wilson L, Burrows F, Shores CG. BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy. Int J Cancer. 2010 Mar 1;126(5):1216-25. PubMed PMID: 19662650.

5: Lundgren K, Zhang H, Brekken J, Huser N, Powell RE, Timple N, Busch DJ, Neely L, Sensintaffar JL, Yang YC, McKenzie A, Friedman J, Scannevin R, Kamal A, Hong K, Kasibhatla SR, Boehm MF, Burrows FJ. BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol Cancer Ther. 2009 Apr;8(4):921-9. PubMed PMID: 19372565.