Development of the proteasome inhihitor Veleade™ (Bortezomib)

被引：550

作者：

Adams, J ^{[1
]}

Kauffman, M ^{[1
]}

机构：

[1] Millennium Pharmaceut Inc, Cambridge, MA USA

来源：

CANCER INVESTIGATION | 2004年 / 22卷 / 02期

关键词：

antineoplastic agents; boronic acids; enzyme inhibitors (administration and dose); NF-KB (antagonists and inhibitors); hematologic neoplasms (drug therapy); multienzyme complexes (antagonists and inhibitors);

D O I：

10.1081/CNV-120030218

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The dipeptide boronic acid analogue VELCADE(TM) (Bortezomib; formerly known as PS-341, LDP-341 and MLM341) is a potent and selective inhibitor of the proteasome, a multicatalytic enzyme that mediates many cellular regulatory signals by degrading regulatory proteins or their inhibitors. The proteasome, is, thus, a potential target for pharmacological agents. Bortezomib, the first proteasome inhibitor to reach clinical trials, has shown in vitro and in vivo activity against a variety of malignancies, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer. The drug is rapidly cleared from the vascular compartment, but a novel pharmacodynamic assay has shown that bortezomib-mediated proteasome blockade is dose-dependent and reversible. Based on phase I studies demonstrating that bortezomib has manageable toxicities in patients with advanced cancers, phase II trials have been initiated for both solid and hematological malignancies.

引用

页码：304 / 311

页数：8

共 52 条

[1] Proteasome inhibition in cancer: Development of PS-341 [J].