Development of TGF-beta signalling inhibitors for cancer therapy.
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.
Yingling
Jonathan M
JM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. yingling_jonathan_m@lilly.com
Blanchard
Kerry L
KL
Sawyer
J Scott
JS
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta