Research Development Foundation

Hudson Institute of Medical Research

Craig A Harrison

Wylie Walker Vale, Jr

Peter C Gray

Senyon Choe

Wolfgang Fischer

Kelly Walton

The present invention relates to inhibin analogs, their method of production and their use in the treatment and prophylaxis of disease or conditions associated with reduced levels of inhibin and activin-mediated signaling.

Inhibin analogs

Cripto, a developmental oncoprotein, antagonizes activin and TGF-b signaling by forming a complex with activin and TGF-b and their type II receptors. This complex precludes the formation of a functional activin/TGF-b&#x2022;type II&#x2022;type I complex, thereby blocking the signaling of activin and TGF-b. Cripto may be generally capable of blocking antiproliferative Smad2/3 signals and provides a novel mechanism of oncogenic action with multiple therapeutic implications. Inhibiting the formation of Cripto and activin/TGF-b complex may enhance antiproliferative effects of activin and TGF-b.

Cripto antagonism of activin and TGF-b signaling

Members of the TGF-&#x3b2; superfamily control many physiologic and pathophysiologic processes in multiple tissues and signal via type II and type I receptor serine kinases. Type II activin receptors are promiscuous and known to bind 12 TGF-&#x3b2; ligands including activins, myostatin, BMPs and nodal. Methods are described for the screening and identification of antagonist for TGF-&#x3b2; superfamily members, in particular activin-A antagonist.

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Nunswading, Australia

Craig A Harrison