Rational discovery of a highly novel and selective mTOR inhibitor

Bioorg Med Chem Lett. 2019 Nov 1;29(21):126659. doi: 10.1016/j.bmcl.2019.126659. Epub 2019 Sep 3.

Abstract

Aided by Structure Based Drug Discovery (SBDD), we rapidly designed a highly novel and selective series of mTOR inhibitors. This chemotype conveys exquisite kinase selectivity, excellent in vitro and in vivo potencies and ADME safety profiles. These compounds could serve as good tools to explore the potential of TORC inhibition in various human diseases.

Keywords: Inhibitor; SBDD; mTOR.

MeSH terms

  • Binding, Competitive
  • Drug Discovery
  • Furans / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Morpholines / chemistry
  • Phosphatidylinositol 3-Kinase / chemistry
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / metabolism*
  • Pyridines / chemistry*
  • Pyrimidines / chemistry*
  • Structure-Activity Relationship
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Furans
  • Morpholines
  • PI103
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrimidines
  • morpholine
  • Phosphatidylinositol 3-Kinase
  • TOR Serine-Threonine Kinases
  • pyrimidine