From allosteric drugs to allo-network drugs: State of the art and trends of design, synthesis, and computational methods

Peter Csermely, Ruth Nussinov, András Szilágyi

Research output: Contribution to journalEditorial

20 Citations (Scopus)

Abstract

Allosteric drugs bind to sites which are usually less conserved evolutionarily as compared to orthosteric sites. As such, they can discriminate between closely related proteins, have fewer side effects, and a consequent lower concentration can convey a lesser likelihood of receptor desensitization. However, an allosteric mode of action may also make the results of preclinical and animal experiments less predictive. The sensitivity of the allosteric consequences to the environment further increases the importance of accounting for patient population diversity. Even subtle differences in protein sequence, in cellular metabolic states or in target tissues, can result in different outcomes. This mini-hot-topic issue of CTMC showcases some successes and challenges of allosteric drug development through the examples of seventransmembrane (GPCR), AMPA, NMDA and metabotropic glutamate receptors, as well as the morpheein model of allosterism involved in inherent metabolic errors. Finally, the development of allo-network drugs, which are allosteric drugs acting indirectly on the neighborhood of the pharmacological target in protein-protein interaction or signaling networks, is described.

Original languageEnglish
Pages (from-to)2-4
Number of pages3
JournalCurrent topics in medicinal chemistry
Volume13
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Allo-network drugs
  • Allosteric drugs
  • Glutamatergic transmission
  • Gpcr receptors
  • Networks
  • Quaternary structure
  • Sar landscapes
  • Schizophrenia

ASJC Scopus subject areas

  • Drug Discovery

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