Target intelligence / Profile preview

Neurokinin-2 Receptor (NK2R)

Target
NK2R
Molecular classification
G protein-coupled receptor, Receptor
01

Overview

The Neurokinin-2 receptor (NK2R), also known as the tachykinin receptor 2 or substance K receptor, is a G protein-coupled receptor (GPCR) that primarily binds the neuropeptide neurokinin A (NKA). It mediates various physiological processes including smooth muscle contraction, regulation of inflammation, and pain transmission. NK2Rs are expressed on various cell types including neurons within both central and peripheral nervous systems, immune cells (macrophages, mast cells, T lymphocytes). Dysregulation of NK2Rs has been implicated in chronic airway diseases and inflammatory disorders. Several antagonists have undergone clinical trials for indications like IBS and depression but have not reached approval due to insufficient efficacy or adverse outcomes.

Other names
Tachykinin Receptor 2Substance K Receptor
02

Mechanism of action

Agonist: activation of G proteins leading to activation of phospholipase C and downstream signaling involving MAPK/ERK pathway, mTOR signaling cascade, and modulation of cytokine expression via transcription factors like AP‑1 and NF‑κB. Antagonist: blockade of receptor activation by endogenous ligand.

03

Biological functions

Smooth muscle contractionRegulation of inflammationPain transmissionSignal transduction
04

Disease associations

AsthmaCOPDMigraine headachesPain syndromesInflammatory disordersIrritable Bowel Syndrome (IBS)Depression
05

Safety considerations

Clinical trials for antagonists have been discontinued due to lack of efficacy or negative results.
06

Interacting drugs

GR-64349

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