Therapeutic uses of smad protein inhibitors: Selective inhibition of specific TGF-beta activities.
Recent advances in TGF-beta signaling biology have identified smad proteins as cytoplasmic mediators of TGF-beta receptor activation. Current evidence suggests that smad proteins are transcription factors whose activity is regulated through phosphorylation by TGF-beta type I receptors. Several isoforms of the smad proteins have been identified which confer in part selectivity for different members of the TGF-beta family of receptors as well as some selectivity for downstream effects of TGF-beta activation. Therefore, smad proteins provide an attractive means for targeting select activities of TGF-beta by either inhibiting their phosphorylation or specific DNA binding modes. Because TGF-beta is a central player in the development of fibrosis, selective inhibition of smad proteins would provide an important therapeutic benefit in many acute and chronic fibrotic diseases.
Laping
N J
NJ
Renal Pharmacology, Smithkline Beecham Pharmaceuticals, 709 Swedeland Road, POB 1539 King of Prussia, PA 19406, USA. nicholas_j_laping@sbphrd.com