Smac mimetics as IAP antagonists

Semin Cell Dev Biol. 2015 Mar:39:132-8. doi: 10.1016/j.semcdb.2014.12.005. Epub 2014 Dec 27.

Abstract

As the Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in human cancers, they represent promising targets for therapeutic intervention. Small-molecule inhibitors of IAP proteins mimicking the endogenous IAP antagonist Smac, called Smac mimetics, neutralize IAP proteins and thereby promote the induction of cell death. Smac mimetics have been shown in preclinical models of human cancer to directly trigger cancer cell death or to sensitize for cancer cell death induced by a variety of cytotoxic stimuli. Smac mimetics are currently undergoing clinical evaluation in phase I/II trials, demonstrating that therapeutic targeting of IAP proteins has reached the clinical stage.

Keywords: Cancer; Cell death; IAP proteins; Smac mimetic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Cell Death / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Neoplasms / drug therapy
  • Oligopeptides / chemistry

Substances

  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • Oligopeptides
  • SMAC peptide