NK1R
Neurokinin-1 receptor (NK1R), encoded by TACR1, is the preferred receptor for substance P and functions as a G protein-coupled receptor that links neuronal, immune, and inflammatory signaling systems[1][2]. Upon substance P binding, NK1R activates phospholipase C-, protein kinase C-, and MAPK-associated pathways, leading to intracellular calcium mobilization, NF-κB activation, and production of pro-inflammatory mediators[2][3]. Mechanistically, the substance P/NK1R axis regulates neurogenic inflammation, immune cell activity, vascular permeability, cytokine production, and cellular responses relevant to pain, stress, and tissue injury[1][2][3]. In disease models, increased NK1R signaling has been associated with neuroinflammation, inflammatory disorders, infection-related pathology, and multiple cancer types, where receptor activation contributes to cell proliferation, migration, angiogenesis, and survival signaling[1][2][4]. Compared with related tachykinin receptors NK2R and NK3R, NK1R exhibits the highest affinity for substance P and possesses two major isoforms, a full-length receptor and a truncated receptor that differ in signaling capacity and biological function[1][5]. The full-length isoform more effectively supports NF-κB-dependent inflammatory signaling, whereas the truncated isoform displays distinct regulatory properties and has been implicated in immune modulation and cancer-associated biology[3][5]. For experimental applications, selective NK1R antagonists have been widely used to investigate substance P-dependent signaling pathways and have demonstrated therapeutic utility in chemotherapy-induced nausea and vomiting, while remaining valuable pharmacological tools for studying inflammation, neurobiology, and tumor-related mechanisms[2][4].
References:
- [1]. Douglas SD, et al. Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation. Ann N Y Acad Sci. 2011 Jan;1217:83-95. [Content Brief]
- [2]. Mishra A, et al. Neurokinin receptors and their implications in various autoimmune diseases. Curr Res Immunol. 2021 Jul 1;2:66-78. [Content Brief]
- [3]. Peter EK, et al. A Hybrid Hamiltonian for the Accelerated Sampling along Experimental Restraints. Int J Mol Sci. 2019 Jan 16;20(2):370. [Content Brief]
- [4]. Garcia-Recio S, et al. Biological and Pharmacological Aspects of the NK1-Receptor. Biomed Res Int. 2015;2015:495704. [Content Brief]
- [5]. Tuluc F, et al. Neurokinin 1 receptor isoforms and the control of innate immunity. Trends Immunol. 2009 Jun;30(6):271-6. [Content Brief]
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NK1R Related Products (64)
Related Products (64)
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Senktide
0 ImagesSenktide is a potent, selective agonist of the neuromedin K3 (NK3) receptor (EC50=0.5-3 nM). Senktide less potently agonizes the NK1 receptor (EC50=35 µM). Senktide is promising for research of neurological disease.
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N-Acetyl-L-tryptophan
0 ImagesN-Acetyl-L-tryptophan is an antagonist of the neurokinin-1 receptor (NK-1R), disrupting the binding of substance P (SP) to NK-1R. This action provides neuroprotective effects, improving memory deficits and motor impairments. N-Acetyl-L-tryptophan is also an inhibitor of cytochrome c (Cytochrome c), and it exerts antioxidant and anti-inflammatory effects by inhibiting the expression of IL-1β and the activation of caspase-1. N-Acetyl-L-tryptophan holds promise for research in neurodegenerative and inflammatory diseases.
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L-733060 hydrochloride
0 ImagesL-733060 hydrochloride is a selective neurokinin-1 (NK-1) receptor antagonist. L-733060 hydrochloride mainly regulates pain transmission and neural plasticity by blocking the binding of Substance P (P substance) to the NK-1 receptor. L-733060 hydrochloride blocks the promoting effect of Substance P on long-term potentiation (LTP) in the hippocampus. L-733060 hydrochloride reverses the orofacial hyperalgesia induced by experimental occlusal interference (EOI) in rats. L-733060 hydrochloride hydrochloride inhibits neurogenic plasma extravasation at a dose that does not cause adverse cardiovascular effects in rodents, and also acts as an anti-tumor agent. L-733060 hydrochloride can be used for the study of chronic orofacial pain.
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Ranakinin
0 ImagesCat. No.: HY-P2139CAS No.: 139446-71-2Ranakinin is a NK1R agonist. Ranakinin inhibits the binding of selective NK1 radioligands to NK1 receptors. Ranakinin activates phospholipase C (Phospholipase C), thereby enhancing polyphosphoinositide hydrolysis. Ranakinin stimulates inositol phosphate production and reduces membrane polyphosphoinositide levels. Ranakinin stimulates corticosterone and aldosterone secretion.
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GR-73632
0 ImagesGR-73632 is a tachykinin NK1 receptor agonist. GR-73632 activates spinal NK1 receptors to induce scratching, biting and licking behaviors. GR-73632 activates peripheral NK1 receptors to trigger lacrimation in guinea pigs, and activates central NK1 receptors to induce repetitive hind paw tapping behavior in gerbils. GR-73632 is applicable to research related to pruritus.
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L-732138
0 ImagesL-732138 is a selective, potent and competitive neurokinin-1 (NK-1) receptor antagonist with an IC50 of 2.3 nM. L-732138 has 200-fold more potent in cloned human NK-1 receptors than cloned rat NK-1 receptors, and has > 1000-fold more potent than human NK-2 and NK-3 receptors. L-732138 can reduce hyperalgesia and has antitumor action.
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Eprazinone dihydrochloride
0 ImagesEprazinone dihydrochloride is a gent with mucolytic, secretolytic, antitussive, and bronchial antispasmodic properties. Eprazinone dihydrochloride is a neurokinin 1 receptor (NK1R) ligand. Eprazinone dihydrochloride has the potential for chronic bronchitis treatment that improved pulmonary function and arterial partial pressure of oxygen.
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Vapreotide
0 ImagesSynonyms: RC160; BMY 41606Vapreotide is a neurokinin-1 (NK1) receptor antagonist, with an IC50 of 330 nM.
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Orvepitant maleate
0 ImagesSynonyms: GW823296 maleateOrvepitant maleate (GW823296 maleate) is potent, selective, orally active and well-tolerated neurokinin-1 receptor (NK-1) antagonist with a pKi of 10.2 for human neurokinin-1 receptor. Orvepitant maleate can across the blood-brain barrier. Orvepitant maleate has the potential for depressive disorder and chronic refractory cough (CRC) treatment.
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Spantide II
0 ImagesSpantide II, an undecapeptide substance P (SP) analog, is a potent neurokinin-1 receptor (NK-1R) antagonist. Spantide II binds with NK-1R and blocks proinflammatory activities associated with SP. Spantide II can be used in the research of inflammatory skin disorders, such as psoriasis and contact dermatitis.
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Rolapitant hydrochloride hydrate
0 ImagesSynonyms: SCH619734 hydrochloride hydrateRolapitant hydrochloride hydrate (SCH619734 hydrochloride hydrate) is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a Ki of 0.66 nM. Rolapitant hydrochloride hydrate does not interact with CYP3A4. Rolapitant hydrochloride hydrate shows potent anti-emetic activity in a ferret emesis model.
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Maropitant
0 ImagesMaropitant is an orally active NK1 receptor antagonist. Maropitant prevents vomiting and inhibits ulcerative dermatitis.
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Casopitant mesylate
0 ImagesSynonyms: GW679769BCasopitant mesylate (GW679769B) is a potent, selective, brain permeable and orally active neurokinin 1 (NK1) receptor antagonist. Casopitant mesylate is a second in the class of antiemetics that acts to antagonise the emetogenic effect of Substance P (HY-P0201). Casopitant mesylate is also a substrate and a weak-to-moderate inhibitor of CYP3A4. Casopitant mesylate can be used for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).
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Vofopitant dihydrochloride
0 ImagesSynonyms: GR 205171AVofopitant dihydrochloride (GR 205171A) is a blood-brain barrier-permeable NK1 receptor inhibitor with a pKi of 9.02 in mice. Vofopitant dihydrochloride blocks vomiting-related responses and inhibits pseudoptyalism. Vofopitant dihydrochloride exerts anxiolytic effects, regulates 5-HT receptor function and increases central 5-HT release. Vofopitant dihydrochloride improves hyperarousal symptoms of post-traumatic stress disorder. Vofopitant dihydrochloride can be used in research related to depression, anxiety, vomiting and postoperative nausea and vomiting.
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Hemokinin 1 (mouse)
0 ImagesHemokinin 1 (mouse) is a selective agonist of neurokinin-1 receptor, with Ki of 0.175 nM and 560 nM for human NK1 receptor and human NK2 receptor, respectively.
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Spantide I
0 ImagesSpantide I, a substance P analog, is a selective NK1 receptor antagonist, with Ki values of 230 nM and 8150 nM for NK1 and NK2 receptor, respectively. Spantide I provides an approach to reduce type 1 and enhance the type 2 cytokine IL-10 in the infected cornea, leading to a significant reduction in corneal perforation.
