Document Report Card

ID: ALA1141651

Journal: J Med Chem

Title: Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer.

Authors: Dorsey BD, Iqbal M, Chatterjee S, Menta E, Bernardini R, Bernareggi A, Cassarà PG, D'Arasmo G, Ferretti E, De Munari S, Oliva A, Pezzoni G, Allievi C, Strepponi I, Ruggeri B, Ator MA, Williams M, Mallamo JP.

Abstract: The ubiquitin-proteasome pathway plays a central role in regulation of the production and destruction of cellular proteins. These pathways mediate proliferation and cell survival, particularly in malignant cells. The successful development of the 20S human proteasome inhibitor bortezomib for the treatment of relapsed and refractory multiple myeloma has established this targeted intervention as an effective therapeutic strategy. Herein, the potent, selective, and orally bioavailable threonine-derived 20S human proteasome inhibitor that has been advanced to preclinical development, [(1R)-1-[[(2 S,3 R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid 20 (CEP-18770), is disclosed.

CiteXplore: 18247547

DOI: 10.1021/jm7010589