Bortezomib

CAT#: H179324-69-7

CAS#: 179324-69-7


Description: Bortezomib is a dipeptide boronic acid analogue 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)-kappaB, a protein that is constitutively activated in some cancers, thereby interfering with NF-kappaB-mediated cell survival, tumor growth, and angiogenesis. In vivo, bortezomib delays tumor growth and enhances the cytotoxic effects of radiation and chemotherapy.

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Synthetic Routes

Bortezomib - Synthetic Route 1

Bortezomib route01

Synthetic reference

Peuchmaur, Marine; Lacour, Marie-Agnes; Sevalle, Jean; Lisowski, Vincent; Touati-Jallabe, Youness; Rodier, Fabien; Martinez, Jean; Checler, Frederic; Hernandez, Jean-Francois. Further characterization of a putative serine protease contributing to the γ-secretase cleavage of β-amyloid precursor protein. Bioorganic & Medicinal Chemistry. Institut des Biomolecules Max Mousseron, UMR5247 CNRS, Faculte de Pharmacie. Universites Montpellier 1 and 2. Montpellier, Fr. 34093. Volume 21. Issue 4. Pages 1018-1029. 2013

Bortezomib - Synthetic Route 2

Bortezomib route02

Synthetic reference

Hinkes, Stefan P. A.; Klein, Christian D. P. Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids. Organic Letters. Institute of Pharmacy and Molecular Biotechnology (IPMB), Medicinal Chemistry. University of Heidelberg. Heidelberg, Germany 69120. Volume 21. Issue 9. Pages 3048-3052. 2019

Bortezomib - Synthetic Route 3

Bortezomib route03

Synthetic reference

Beenen, Melissa A.; An, Chihui; Ellman, Jonathan A. Asymmetric copper-catalyzed synthesis of α-amino boronate esters from N-tert-butanesulfinyl aldimines. Journal of the American Chemical Society. Department of Chemistry. University of California. Berkeley, USA 94720. Volume 130. Issue 22. Pages 6910-6911. 2008

Bortezomib - Synthetic Route 4

Bortezomib route04

Synthetic reference

Zhu, Yongqiang; Zhao, Xin; Zhu, Xinrong; Wu, Gang; Li, Yuejie; Ma, Yuheng; Yuan, Yunxia; Yang, Jie; Hu, Yang; Ai, Li; Gao, Qingzhi. Design, Synthesis, Biological Evaluation, and Structure-Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of α-Amino Acid Boronates. Journal of Medicinal Chemistry. Jiangsu Simcere Pharmaceutical Research Institute and Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research. Nanjing, Peop. Rep. China 210042. Volume 52. Issue 14. Pages 4192-4199. 2009

Bortezomib - Synthetic Route 5

Bortezomib route05

Synthetic reference

Xie, Jian-Bo; Luo, Jian; Winn, Timothy R.; Cordes, David B.; Li, Guigen. Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines. Beilstein Journal of Organic Chemistry. Department of Chemistry and Biochemistry. Texas Tech University. Lubbock, USA 79409-1061. Volume 10. Pages 746-751, 6 pp.2014

Bortezomib - Synthetic Route 6

Bortezomib route06

Synthetic reference

Lei, Meng; Zhao, Xin; Wang, Zhanli; Zhu, Yongqiang. Pharmacophore Modeling, Docking Studies, and Synthesis of Novel Dipeptide Proteasome Inhibitors Containing Boron Atoms. Journal of Chemical Information and Modeling. College of Science. Nanjing Forestry University. Nanjing, Peop. Rep. China 210037. Volume 49. Issue 9. Pages 2092-2100. 2009

Bortezomib - Synthetic Route 7

Bortezomib route07

Synthetic reference

Daniels, Blake E.; Stivala, Craig E. A solid-phase approach for the synthesis of α-aminoboronic acid peptides. RSC Advances. Discovery Chemistry. Genentech, Inc.. South San Francisco, USA 94080. Volume 8. Issue 6. Pages 3343-3347. 2018

Bortezomib - Synthetic Route 8

Bortezomib route08

Synthetic reference

Gao, De-Wei; Gao, Yang; Shao, Huiling; Qiao, Tian-Zhang; Wang, Xin; Sanchez, Brittany; Chen, Jason S.; Liu, Peng; Engle, Keary M. Cascade CuH-catalyzed conversion of alkynes to enantioenriched 1,1-disubstituted products. ChemRxiv. Department of Chemistry. The Scripps Research Institute. La Jolla, USA 92037. Pages 1-7. 2019

Bortezomib - Synthetic Route 9

Bortezomib route09

Synthetic reference

Chen, Bo; Huang, Yu. Synthesis of antitumor drug bortezomib. Huaxue Yu Shengwu Gongcheng. Chongqing Taihao Pharmaceutical Co., Ltd. Chongqing, Peop. Rep. China 400039. Volume 31. Issue 6. Pages 42-44. 2014

Bortezomib - Synthetic Route 10

Bortezomib route010

Synthetic reference

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. Assignee Dr. Reddy's Laboratories Ltd., India; Dr. Reddy's Laboratories, Inc.WO 2009036281. 2009