Smoothened polypeptides and methods of use

US8546524B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Nadya I. Tarasova · Frederick, US
• Michael Dean · Frederick, US
• Hong Lou · Frederick, US

Key dates

• Filing date: May 14, 2012
• Grant date: Oct 1, 2013
• Expiry date: May 14, 2032

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P43/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed is an isolated or purified polypeptide or peptidomimetic comprising an amino acid sequence of a portion of a Smoothened (SMO) protein, wherein the portion comprises an amino acid sequence of any of the intracellular loops of the SMO protein, a functional fragment thereof, or a functional variant of either the portion or the functional fragment, wherein the functional fragment comprises at least 7 contiguous amino acids of the intracellular loops, and wherein the functional fragment or functional variant inhibits proliferation of a diseased cell, or a fatty acid derivative thereof. Related conjugates, nucleic acids, recombinant expression vectors, host cells, and pharmaceutical compositions are further provided. Methods of inhibiting proliferation of a diseased cell, treating or preventing cancer, treating a neoplasm or psoriasis, and inhibiting the expression of genes involved in the Hedgehog signaling pathway, thereby inhibiting the Hedgehog signaling pathway, are furthermore provided by the invention.