mTORC1-Specific Peptide Inhibitor for Metabolic Diseases

SK2014-037

SUMMARY OF INVENTION

The protein mTORC1 (mechanistic target of rapamycin complex 1) controls cell growth, dysregulation of which has been associated with a variety of diseases including aging, diabetes, and cancer.  Overactivation of mTORC1 signaling has been shown to induce adipogenesis as well as decrease insulin sensitivity, resulting in diabetes.  Rapamycin is a well-characterized inhibitor of both mTORC1 and mTORC2 proteins.  While effective as a cancer therapy, chronic rapamycin treatment has been shown to decrease insulin sensitivity and cause side effects such as immunosuppression in vivo, potentially as a result of mTORC2 inhibition.  Thus, mTORC1-specific inhibitors could serve as therapies for diabetes and other metabolic diseases.  

MSK investigators have generated a cell-permeable peptide that inhibits mTORC1 but does not inhibit  mTORC2.  This peptide is capable of suppressing mTORC1 signaling through a nutrient-sensing pathway (Rag GTPase) in cultured cells.

ADVANTAGES

  • The first mTORC1-specific peptide inhibitor
  • Potentially fewer side effects compared to small molecule mTOR inhibitors such as rapamycin, which inhibit both mTORC1 and mTORC2
  • Therapeutic potential to address a number of significant metabolic diseases

MARKET OPPORTUNITY

Metabolic diseases such as diabetes and obesity

STAGE OF DEVELOPMENT

In vitro data

PATENT INFORMATION

PCT application PCT/US2015/051875 filed on September 24, 2015

PUBLICATION

Peng M, Yin N, Li MO. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell. 2014 Sep 25;159(1):122-33

LEAD INVESTIGATOR

Ming Li, PhD, Laboratory Head, Immunology Program, Memorial Sloan Kettering

CONTACT INFORMATION

Eileen Flowers, PhD, Licensing Manager, Tel: 646-888-1067, E-mail: flowerse@mskcc.org

Stage of Development

In vitro