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Target intelligence / Profile preview
Endothelin-3 (EDN3)
- Target
- EDN3
- Molecular classification
- Endogenous ligand, Hormone (vasoactive peptide), Secreted peptide
01
Overview
Endothelin-3 is a 21-amino-acid, endothelium-derived vasoactive peptide processed from a precursor protein; it is a member of the endothelin family, which includes ET-1 and ET-2. Its primary function is to act as a ligand for endothelin receptor type B (EDNRB), where it is essential for the terminal migration and localization of melanocytes and enteric neurons. Mutations in EDN3 or its receptor cause congenital disorders such as Hirschsprung disease (intestinal aganglionosis) and Waardenburg syndrome (pigmentary abnormalities with deafness). Endothelin-3 is involved in signal transduction, cell migration, and proliferation. Expression or function may be altered in tumors and may impact additional vascular or developmental diseases.
- Other names
- ET-3PPET3ET3Preproendothelin-3HSCR4WS4Bendothelin 3EDN3
02
Mechanism of action
Competitive antagonism at endothelin receptor B (ETNRB); Modulation of signal transduction pathways for cell migration and differentiation
03
Biological functions
Ligand for G protein-coupled receptor (EDNRB)Regulation of neural crest cell migrationRegulation of melanocyte developmentRegulation of enteric neuron developmentSignal transductionVascular homeostasis
04
Disease associations
Hirschsprung disease (congenital aganglionic megacolon)Waardenburg syndrome (type IV)Tumorigenesis (impaired or altered expression implicated in cancer)Potentially cardiovascular and renal disease (by analogy with other endothelins)
05
Safety considerations
Pharmacological inhibition of endothelin signaling may impair neural or pigment cell developmentPotential impact on vascular tone and blood pressure if systemically modulated
06
Interacting drugs
Endothelin receptor antagonists (e.g., bosentan, which blocks ETA and ETB, but ETNRB specificity would affect EDN3)
07
Biomarkers
Mutations in EDN3 (and EDNRB) are biomarkers for Hirschsprung disease and Waardenburg syndrome (type IV)Expression/epigenetic silencing in tumor tissues
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