WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200505
CAS#: 848695-25-0 (free base)
Description: BIIB021, also known as CNF2024, 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.
MedKoo Cat#: 200505
Name: BIIB021
CAS#: 848695-25-0 (free base)
Chemical Formula: C14H15ClN6O
Exact Mass: 318.09959
Molecular Weight: 318.76
Elemental Analysis: C, 52.75; H, 4.74; Cl, 11.12; N, 26.36; O, 5.02
Related CAS #: 1225041-97-3 (mesylate) 848695-25-0 (free base)
Synonym: BIIB021; BIIB 021; BIIB-021; CNF-2024; CNF 2024; CNF2024.
IUPAC/Chemical Name: [6-Chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-yl]amine
InChi Key: QULDDKSCVCJTPV-UHFFFAOYSA-N
InChi Code: InChI=1S/C14H15ClN6O/c1-7-4-17-9(8(2)11(7)22-3)5-21-6-18-10-12(15)19-14(16)20-13(10)21/h4,6H,5H2,1-3H3,(H2,16,19,20)
SMILES Code: NC1=NC(Cl)=C2N=CN(CC3=NC=C(C)C(OC)=C3C)C2=N1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | BIIB021 (CNF2024) is a synthetic inhibitor of HSP90 with a Ki and an EC50 of 1.7 nM and 38 nM, respectively. |
| In vitro activity: | To address whether BIIB021 can promote the degradation of polyQ-expanded ATXN1, this study treated N2a cells expressing the wild-type (ATXN1 [2Q]) or mutant ATXN1 (ATXN1 [84Q]) with the indicated doses of BIIB021 for 24 h. Immunoblot analysis showed a dose-dependent decline in mutant ATXN1 expression after treatment with BIIB021 (63.8% at 100 nM, P <0.001), whereas the levels of wild-type ATXN1 were not significantly altered (P = 0.146), suggesting that the mutant ATXN1 is sensitive to BIIB021 (Fig. 1A, B). Reference: Neuroscience. 2016 Jul 7;327:20-31. https://pubmed.ncbi.nlm.nih.gov/27058144/ |
| In vivo activity: | Finally, this study investigated the effect of BIIB021 using an NOG mouse xenograft model (Figure 6). NOG mice are completely immunodeficient and can accept the EBV-positive NK cell line SNK6. When this study inoculated SNK6 cells subcutaneously, tumors developed rapidly. After the subcutaneous inoculation of SNK6, this study administered BIIB021 orally and measured the tumor volumes. BIIB021 inhibited the growth of EBV-positive NK cell lymphomas compared with the results in control mice (p < 0.05). Reference: Front Microbiol. 2015; 6: 280. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391044/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 42.72 | 134.02 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.57 | |
| DMF | 30.0 | 94.11 | |
| Ethanol | 2.0 | 6.27 |
The following data is based on the product molecular weight 318.76 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Ding Y, Adachi H, Katsuno M, Sahashi K, Kondo N, Iida M, Tohnai G, Nakatsuji H, Sobue G. BIIB021, a synthetic Hsp90 inhibitor, induces mutant ataxin-1 degradation through the activation of heat shock factor 1. Neuroscience. 2016 Jul 7;327:20-31. doi: 10.1016/j.neuroscience.2016.03.064. Epub 2016 Apr 4. PMID: 27058144. 2. He W, Ye X, Huang X, Lel W, You L, Wang L, Chen X, Qian W. Hsp90 inhibitor, BIIB021, induces apoptosis and autophagy by regulating mTOR-Ulk1 pathway in imatinib-sensitive and -resistant chronic myeloid leukemia cells. Int J Oncol. 2016 Apr;48(4):1710-20. doi: 10.3892/ijo.2016.3382. Epub 2016 Feb 8. PMID: 26892093. 3. Suzuki M, Takeda T, Nakagawa H, Iwata S, Watanabe T, Siddiquey MN, Goshima F, Murata T, Kawada J, Ito Y, Kojima S, Kimura H. The heat shock protein 90 inhibitor BIIB021 suppresses the growth of T and natural killer cell lymphomas. Front Microbiol. 2015 Apr 9;6:280. doi: 10.3389/fmicb.2015.00280. PMID: 25914683; PMCID: PMC4391044. 4. Gopalakrishnan R, Matta H, Chaudhary PM. A purine scaffold HSP90 inhibitor BIIB021 has selective activity against KSHV-associated primary effusion lymphoma and blocks vFLIP K13-induced NF-κB. Clin Cancer Res. 2013 Sep 15;19(18):5016-26. doi: 10.1158/1078-0432.CCR-12-3510. Epub 2013 Jul 23. PMID: 23881928; PMCID: PMC3804723. |
| In vitro protocol: | 1. Ding Y, Adachi H, Katsuno M, Sahashi K, Kondo N, Iida M, Tohnai G, Nakatsuji H, Sobue G. BIIB021, a synthetic Hsp90 inhibitor, induces mutant ataxin-1 degradation through the activation of heat shock factor 1. Neuroscience. 2016 Jul 7;327:20-31. doi: 10.1016/j.neuroscience.2016.03.064. Epub 2016 Apr 4. PMID: 27058144. 2. He W, Ye X, Huang X, Lel W, You L, Wang L, Chen X, Qian W. Hsp90 inhibitor, BIIB021, induces apoptosis and autophagy by regulating mTOR-Ulk1 pathway in imatinib-sensitive and -resistant chronic myeloid leukemia cells. Int J Oncol. 2016 Apr;48(4):1710-20. doi: 10.3892/ijo.2016.3382. Epub 2016 Feb 8. PMID: 26892093. |
| In vivo protocol: | 1. Suzuki M, Takeda T, Nakagawa H, Iwata S, Watanabe T, Siddiquey MN, Goshima F, Murata T, Kawada J, Ito Y, Kojima S, Kimura H. The heat shock protein 90 inhibitor BIIB021 suppresses the growth of T and natural killer cell lymphomas. Front Microbiol. 2015 Apr 9;6:280. doi: 10.3389/fmicb.2015.00280. PMID: 25914683; PMCID: PMC4391044. 2. Gopalakrishnan R, Matta H, Chaudhary PM. A purine scaffold HSP90 inhibitor BIIB021 has selective activity against KSHV-associated primary effusion lymphoma and blocks vFLIP K13-induced NF-κB. Clin Cancer Res. 2013 Sep 15;19(18):5016-26. doi: 10.1158/1078-0432.CCR-12-3510. Epub 2013 Jul 23. PMID: 23881928; PMCID: PMC3804723. |
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.
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.).
(source: Mol Cancer Ther. 2009 Apr;8(4):921-9.).
