University of Texas System

Baylor College of Medicine

Tufts College

Beth Levine

Olivier Lichtarge

Angela D Wilkins

Sanae Shoji-Kawata

Jef De Brabander

Qiren Liang

Nick V Grishin

Lisa N Kinch

Wei-Chung Chiang

Richard C Wang

Joshua A Kritzer

Leila Peraro

Yongjie Wei

Small molecule disruptors of Beclin-1/Bc1-2 protein-protein interactions induce autophagy and hence are useful for treating a variety of indications where stimulation of autophagy is therapeutically useful, including cancer, infection immunity, neurodegeneration, longevity.

Small molecule inducers of autophagy

Small molecule disruptors of Beclin-1/Bcl-2 protein-protein interactions induce autophagy and hence are useful for treating a variety of indications where stimulation of autophagy is therapeutically useful, including cancer, infection immunity, neurodegeneration, longevity.

Disclosed herein are cyclic peptides that induce cellular autophagy and have significant cell penetration activity. Methods for inducing autophagy and thereby treating various diseases and conditions associated with impaired autophagy are provided.

Cyclic peptide epitopes and small-molecule mimics for inducing autophagy

An autophagy-inducing compound comprises an autophagy-inducing peptide comprising Beclin 1 peptides immediately N- and C-terminally flanked by moieties Rand R, respectively, wherein up to six of said peptide residues may be substituted, Rand Rdo not naturally flank the Beclin 1 residues, and F270 and F274 are optionally substituted and optionally linked. The compounds may be used to induce autophagy.

Autophagy-inducing peptide analogs

Antibodies specific for human Beclin 1 protein phosphorylated Ser234, Ser295, Tyr229, Tyr233 or Try352 are useful in diagnosing diseases such as cancer and impaired autophagy. The invention further relates to human Beclin 1 mutated at Ser234, Ser295, Tyr229, Tyr233 or Try352 with a phospho-silencing residue and uses thereof.

Beclin 1 phosphorylation

An autophagy-inducing compound comprises an autophagy-inducing peptide comprising Beclin 1 residues 269-279 immediately N- and C-terminally flanked by moieties Rand R, respectively, wherein up to six of said residues may be substituted, Rand Rdo not naturally flank the Belclin 1 residues, and F270 and F274 are optionally substituted and optionally linked. The compounds may be used to induce autophagy.

An autophagy-inducing compound comprises an autophagy-inducing peptide comprising beclin-1 residues 269-283 and a heterologous moiety that promotes therapeutic stability or delivery of the compound. The compound may be used to induce autophagy and in assays with beclin-1 binding partners.

Growing community of inventors

Dallas, TX, United States of America

Beth Levine