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.
- 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
Metabolic diseases such as diabetes and obesity
In vitro data
PCT application PCT/US2015/051875 filed on September 24, 2015
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
Ming Li, PhD, Laboratory Head, Immunology Program, Memorial Sloan Kettering
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