BIIB021, Free Base **

产品名称：BIIB021, Free Base
产品货号：LC  B-7100
产品规格：10 MG
BIIB021 is an orally available, synthetic small-molecule Hsp90 inhibitor.  It binds in the ATP-binding pocket of Hsp90 (Ki = 1.7 ± 0.4 nM) and induces HER-2 degradation with an EC50 of 38 ± 10 nM in MCF-7 cells.  It induces the degradation of client proteins (HER2, pHER2, IGFR-1R, AKT, pAKT, Raf1, pRaf, Cdk4, Cdk6, cyclinD, ER, and PR), increases expression of the heat shock proteins Hsp90α and Hsp70, but has no effect on expression of the nonclient protein phosphatidylinositol 3-kinase p85 subunit.  BIIB021 inhibits the proliferation of N87, MCF-7, and BT474 tumor cells with IC50 values of 0.06, 0.31, and 0.14 µM, respectively.  It has significant antitumor activity in N87 stomach, BT474 breast, CWR22 prostate, U87 glioblastoma, SKOV3 ovarian, and Panc-1 pancreatic tumor xenograft models.  Lundgren K., et al.  "BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90."  Mol. Cancer Ther. 8:  921-929 (2009).
A Phase I clinical trail demonstrated that BIIB021 was generally well tolerated in patients with advanced solid tumors or chronic lymphocytic leukemia.  The maximum tolerated dose of BIIB021 was less than 800 mg twice a week.  Serum and intracellular Hsp70 was increased and the serum level of Her-2/neu extracellular domain was decreased after administration.  The half-life of BIIB021 was about 1 hr.  Elfiky A., et al.  "BIIB021, an oral, synthetic non-ansamycin Hsp90 inhibitor:  Phase I experience."  J. Clin. Oncol. 26:  2503 (2008).
BIIB021 enhanced radiosensitivity of head and neck squamous cell carcinoma (HNSCCA) in vitro and improved the efficacy of radiation in vivo, indicating BIIB021 may be used in HNSCCA patients as a radiosensitizer.  Yin X., et al.  "BIIB021, a novel Hsp90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy."  Int. J. Cancer. 126:  1216-1225 (2010).
BIIB021 inhibited the proliferation of P-gp and/or MRP-1 expressing cancer cell lines.  The cytotoxic activity of BIIB021 was also not influenced by loss of NQO1 or Bcl-2 overexpression.  Compared to 17-AAG, BIIB021 has broader applications against tumors with acquired multidrug resistance.  Zhang H., et al.  "BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance."  Int. J. Cancer. 126:  1226-1234 (2010).
BIIB021 has antitumor activity in Hodgkin's lymphoma in vitro and in vivo.  BIIB021 selectively induced Hodgkin's lymphoma cell death but did not kill normal lymphocytes from healthy individuals.  BIIB021 inhibited the activity of NF-κB, which was independent of IκB mutations.  BIIB021 sensitized Hodgkin's lymphoma cells to NK cell-mediated killing, possibly by increasing the expression of some ligands engaging activating NK cell receptors.  Böll B., et al.  "Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-κB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity."  Clin. Cancer Res. 15:  5108-5116 (2009).
Our BIIB021 product is the free base whose CAS number is given above.  The CAS number of the hydrochloride salt is 848696-06-0.
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.
Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO.  Disposal:  A

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