Development of TGF-β signalling inhibitors for cancer therapy

被引：466

作者：

Yingling, JM ^{[1
]}

Blanchard, KL ^{[1
]}

Sawyer, JS ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2004年 / 3卷 / 12期

关键词：

D O I：

10.1038/nrd1580

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The transforming growth factor-beta (TGF-beta) superfamily of ligands has a pivotal role in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-beta, almost 20 years ago, there have been tremendous advances in our understanding of the complex biology of this superfamily. Deregulation of TGF-beta has been implicated in the pathogenesis of a variety of diseases, including cancer and fibrosis. Here we present the rationale for evaluating TGF-beta signalling inhibitors as cancer therapeutics, the structures of small-molecule inhibitors that are in development and the targeted drug discovery model that is being applied to their development.

引用

页码：1011 / 1022

页数：12

共 119 条

[81] Integration of Smad and Forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation [J].

Seoane, J ;

Le, HV ;

Shen, LJ ;

Anderson, SA ;

Massagué, J .

CELL, 2004, 117 (02) :211-223

[82] Cooperation of the ErbB2 receptor and transforming growth factor β in induction of migration and invasion in mammary epithelial cells [J].

Seton-Rogers, SE ;

Lu, Y ;

Hines, LM ;

Koundinya, M ;

LaBaer, J ;

Muthuswamy, SK ;

Brugge, JS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (05) :1257-1262

[83] Preoperative plasma levels of transforming growth factor beta1 (TGF-β1) strongly predict progression in patients undergoing radical prostatectomy [J].

Shariat, SF ;

Shalev, M ;

Menesses-Diaz, A ;

Kim, IY ;

Kattan, MW ;

Wheeler, TM ;

Slawin, KM .

JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (11) :2856-2864

[84] Mechanisms of TGF-β signaling from cell membrane to the nucleus [J].

Shi, YG ;

Massagué, J .

CELL, 2003, 113 (06) :685-700

[85]

SHULL, NATURE, V359, P693

[86] Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer [J].

Siegel, PM ;

Massagué, J .

NATURE REVIEWS CANCER, 2003, 3 (11) :807-820

[87] Transforming growth factor β signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis [J].

Siegel, PM ;

Shu, WP ;

Cardiff, RD ;

Muller, WJ ;

Massagué, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (14) :8430-8435

[88]

Singh J, 2004, CURR OPIN DRUG DISC, V7, P437

[89] Successful shape-based virtual screening:: The discovery of a potent inhibitor of the type I TGFβ receptor kinase (TβRI) [J].

Singh, J ;

Chuaqui, CE ;

Boriack-Sjodin, PA ;

Lee, WC ;

Pontz, T ;

Corbley, MJ ;

Cheung, HK ;

Arduini, RM ;

Mead, JN ;

Newman, MN ;

Papadatos, JL ;

Bowes, S ;

Josiah, S ;

Ling, LE .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (24) :4355-4359

[90] Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. [J].

Slamon, DJ ;

Leyland-Jones, B ;

Shak, S ;

Fuchs, H ;

Paton, V ;

Bajamonde, A ;

Fleming, T ;

Eiermann, W ;

Wolter, J ;

Pegram, M ;

Baselga, J ;

Norton, L .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (11) :783-792

← 3 4 5 6 7 8 9 10 11 12 →