产品说明书

Oprozomib

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Chemical Structure| 935888-69-0 同义名 : PR-047;ONX 0912
CAS号 : 935888-69-0
货号 : A720176
分子式 : C25H32N4O7S
纯度 : 99%+
分子量 : 532.609
MDL号 : MFCD25976563
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(93.88 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • 20S proteasome

    20S proteasome LMP7, IC50:82 nM

    20S proteasome β5, IC50:36 nM
描述 The proteasome is a multicatalytic protease complex consisted of a 20S proteolytic core and two 19S regulatory caps that assemble with the core at either end to form a 26S complex. The proteasome is responsible for the ubiquitin-dependent turnover of cellular proteins and regulates cell proliferation and survival pathways. Oprozomib is a tripeptide proteasome inhibitor that selectively inhibits chymotrypsin-like activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) with IC50 values of 36nM and 82nM, respectively. In vitro, oprozomib inhibited cell viability of a pair of uterine sarcoma tumor cell lines MES(MDR-) and MES(MDR+) with IC50 values of 25nM and 1322nM, respectively[2]. Oprozomib inhibited the growth of UMSCC-1, CALL33, carfilzomib-resistant UMSCC-1 and carfilzomib-resistant CAL33 cell lines with IC50 values of 88.2nM, 59.3nM, 2294nM and 1112nM, respectively[3]. In addition, oprozomib inhibited the breast cancer cell lines MDA-MB-231 and BT-549 with IC50 values of 0.079μM and 0.05μM, respectively. Oprozomib also increased doxorubicin-induced cytotoxic effects and apoptosis by enhancing doxorubicin-induced JNK/p38/ MAPK phosphorylation in the breast cancer cell lines MDA-MB-231 and BT-549[4]. In vivo, oral administration of oprozomib at 30mg/kg resulted in more than 80% proteasome inhibition in blood, liver and adrenal gland, and elicited an antitumor response equivalent to intravenously administered carfilzomib in RL cells and CT26 cells mouse xenograft models[2].
作用机制 Oprozomib elicits potent pharmacological actions by forming a covalent bond with the active site N-terminal threonine of the 20S proteasome.[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.88mL

0.38mL

0.19mL

9.39mL

1.88mL

0.94mL

18.78mL

3.76mL

1.88mL
参考文献

[1]Chauhan D, Singh AV, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.

[2]Zhou H, Aujay M, Bennett M K, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). Journal of Medicinal Chemistry, 2009, 52(9): 3028-3038

[3]Zang Y, Kirk C J, Johnson D E, et al. Carfilzomib and oprozomib synergize with histone deacetylase inhibitors in head and neck squamous cell carcinoma models of acquired resistance to proteasome inhibitors. Cancer Biology & Therapy, 2014, 15(9): 1142-1152

[4]Shi Y, Bieerkehazhi S, Ma H, et al. Next-generation proteasome inhibitor oprozomib enhances sensitivity to doxorubicin in triple-negative breast cancer cells. International Journal of Clinical and Experimental Pathology, 2018, 11(5): 2347-2355