Nature Communications (Jul 2019)

A novel rapamycin analog is highly selective for mTORC1 in vivo

  • Katherine H. Schreiber,
  • Sebastian I. Arriola Apelo,
  • Deyang Yu,
  • Jacqueline A. Brinkman,
  • Michael C. Velarde,
  • Faizan A. Syed,
  • Chen-Yu Liao,
  • Emma L. Baar,
  • Kathryn A. Carbajal,
  • Dawn S. Sherman,
  • Denise Ortiz,
  • Regina Brunauer,
  • Shany E. Yang,
  • Stelios T. Tzannis,
  • Brian K. Kennedy,
  • Dudley W. Lamming

DOI
https://doi.org/10.1038/s41467-019-11174-0
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 12

Abstract

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Rapamycin extends lifespan in model organisms by targeting mTORC1, but exerts off-target side effects via inhibition of mTORC2. Here, the authors report the identification of a selective mTORC1 inhibitor, and show that it inhibits mTORC1 activity both in vitro and in vivo, with reduced side effects on glucose homeostasis, lipid metabolism, and the immune system.