Semaphorins and plexins as therapeutic targets

Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337.


Semaphorins are membrane-bound or diffusible factors that regulate key cellular functions and are involved in cell-cell communication. Most of the effects of semaphorins are mediated by plexins. Work over the past decade has revealed crucial functions of the semaphorin-plexin system in mammalian physiology. It has also become clear that semaphorins and plexins have important roles in many pathophysiological processes, including cancer, immunological diseases and bone disorders, and that they represent novel targets for drugs to prevent or treat various diseases. This Review summarizes the functions of the mammalian semaphorin-plexin system as well as its role in diseases and discusses emerging strategies to pharmacologically target semaphorin-plexin signalling.

Trial registration: NCT01313065 NCT01764737.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Diseases / physiopathology
  • Bone and Bones / physiology
  • Cell Adhesion Molecules / physiology*
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Central Nervous System / physiology
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Nerve Regeneration / physiology
  • Nerve Tissue Proteins / physiology*
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology
  • Semaphorins / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Semaphorins
  • plexin

Associated data