ATP-competitive inhibitors of the mammalian target of rapamycin: Design and synthesis of highly potent and selective pyrazolopyrimidines Academic Article uri icon

Overview

MeSH Major

  • Adenosine Triphosphate
  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • Protein-Serine-Threonine Kinases
  • Pyrazoles
  • Pyrimidines

abstract

  • The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

publication date

  • August 27, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1021/jm900851f

PubMed ID

  • 19645448

Additional Document Info

start page

  • 5013

end page

  • 6

volume

  • 52

number

  • 16