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BIOLOGICAL INFO
Solubility:
DMSO
Application(s):
Proteasome inhibitor
Form:
Free base
Research Area:
solid tumours, non-small cell lung cancer
REVIEW Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. As a dipeptide boronic acid analog with antineoplastic activity, Bortezomib reversibly inhibits the 26S proteasome, a large protease complex that degrades ubiquinated proteins. By blocking the targeted proteolysis normally performed by the proteasome, bortezomib disrupts various cell signaling pathways, leading to cell cycle arrest, apoptosis, and inhibition of angiogenesis. Specifically, the agent inhibits nuclear factor NF-κB, a protein that is constitutively activated in some cancers, thereby interfering with NF-κB -mediated cell survival, tumor growth, and angiogenesis. In vivo, bortezomib delays tumor growth and enhances the cytotoxic effects of radiation and chemotherapy.
REFERENCES
[1]
Janca, Michal; Dobrovolny, Petr Preparation of bortezomib, a boronic acid dipeptide PCT Int. Appl. (2009), WO 2009004350 A1 20090108.
[2]
Palle, Raghavendracharyulu Venkata; Kadaboina, Rajasekhar; Murki, Veerender; Manda, Amarendhar; Gunda, Nageshwar; Pulla, Ramaseshagiri Rao; Hanmanthu, Mallesha; Mopidevi, Narasimha Naidu; Ramdoss, Suresh Kumar Preparation of bortezomib in crystalline form PCT Int. Appl. (2009), WO 2009036281 A2 20090319.
[3]
Zhu, Yongqiang; Zhao, Xin; Zhu, Xinrong; Wu, Gang; Li, Yuejie; Ma, Yuheng; Yuan, Yunxia; Yang, Jie; Hu, Yang; Ai, Li; et al Design, Synthesis, Biological Evaluation, and Structure-Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of a-Amino Acid Boronates Journal of Medicinal Chemistry (2009), 52(14), 4192-4199.
[4]
Milo, Lawrence J.; Lai, Jack H.; Wu, Wengen; Liu, Yuxin; Maw, Hlaing; Li, Youhua; Jin, Zhiping; Shu, Ying; Poplawski, Sarah E.; Wu, Yong; et al Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors Journal of Medicinal Chemistry (2011), 54(13), 4365-4377.
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