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

被引：129

作者：

Dorsey, Bruce D. ^{[1
]}

Iqbal, Mohamed ^{[1
]}

Chatterjee, Sankar ^{[1
]}

Menta, Ernesto ^{[2
]}

Bernardini, Raffaella ^{[2
]}

Bernareggi, Alberto ^{[2
]}

Cassara, Paolo G. ^{[2
]}

D'Arasmo, Germano ^{[2
]}

Ferretti, Edmondo ^{[2
]}

De Munari, Sergio ^{[2
]}

Oliva, Ambrogio ^{[2
]}

Pezzoni, Gabriella ^{[2
]}

Allievi, Cecilia ^{[2
]}

Strepponi, Ivan ^{[2
]}

Ruggeri, Bruce ^{[1
]}

Ator, Mark A. ^{[1
]}

Williams, Michael ^{[1
]}

MallamoT, John P. ^{[1
]}

机构：

[1] Cephalon Inc, W Chester, PA 19380 USA

[2] Cell Therapeut Europe SRL, I-20091 Bresso, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 04期

关键词：

D O I：

10.1021/jm7010589

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]-1-oxobutyl]amino]-3-methylbutyl]boronic acid 20 (CEP-18770), is disclosed.

引用

收藏

页码：1068 / 1072

页数：5

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