Nav1.7
NaV1.7, encoded by SCN9A, is a voltage-gated sodium channel strongly linked to human nociception, because loss-of-function mutations cause congenital inability to experience pain[1]. Mechanistically, NaV1.7 supports nociceptor excitability and pain signaling, and human studies show that NaV1.7 loss can produce a profound loss of functional nociceptors[2]. In disease models and inherited pain syndromes, gain-of-function SCN9A mutations are associated with paroxysmal extreme pain disorder and related painful phenotypes[3]. Compared with related isoforms, human dorsal root ganglion neurons show higher NaV1.7 expression and lower NaV1.8 expression than mouse dorsal root ganglion neurons, which is relevant for translational pain research[4]. For experimental applications, inflammatory mediators such as NGF and IL-6 sensitize adult dorsal root ganglion neurons, and combined NaV1.7/NaV1.8 blockade strongly affects thermally evoked firing[5]. Structural studies of NaV1.7 antagonists map drug-binding sites and support rational inhibitor design[6].
References:
- [1]. Cox JJ, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006 Dec 14;444(7121):894-8. [Content Brief]
- [2]. McDermott LA, et al. Defining the Functional Role of NaV 1.7 in Human Nociception. Neuron. 2019 Mar 6;101(5):905-919.e8. [Content Brief]
- [3]. Fertleman CR, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron. 2006 Dec 7;52(5):767-74. [Content Brief]
- [4]. Chang W, et al. Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel. Neurosci Bull. 2018 Feb;34(1):4-12. [Content Brief]
- [5]. Atmaramani RR, et al. Conserved Expression of Nav1.7 and Nav1.8 Contribute to the Spontaneous and Thermally Evoked Excitability in IL-6 and NGF-Sensitized Adult Dorsal Root Ganglion Neurons In Vitro. Bioengineering (Basel). 2020 May 16;7(2):44. [Content Brief]
- [6]. Wu Q, et al. Structural mapping of Nav 1.7 antagonists. Nat Commun. 2023 Jun 3;14(1):3224. [Content Brief]
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Nav1.7 Related Products (64)
Related Products (64)
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AZ194
0 ImagesAZ194 is a first-in-class, orally active inhibitor of CRMP2-Ubc9 interaction and inhibitor of NaV1.7 (IC50=1.2 μM). AZ194 blocks SUMOylation of CRMP2 to selectively reduce the amount of surface-expressed NaV1.7. Antinociceptive effects.
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Nav1.7-IN-3
0 ImagesNav1.7-IN-3 is a selective, orally bioavailable voltage-gated sodium channel Nav1.7 inhibitor with an IC50 of 8 nM. Pain relief. Limited CNS penetration.
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3'-Methoxydaidzein
0 Images3'-Methoxydaidzein is a isoflavone and a Sodium Channel inhibitor. 3'-Methoxydaidzein inhibits subtypes NaV1.7, NaV1.8 and NaV1.3 with IC50 of 181 nM, 397 nM, and 505 nM, respectively. 3'-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels.
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Huwentoxin-IV TFA
0 ImagesCat. No.: HY-P1220APurity: 99.18%Huwentoxin-IV TFA is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC50s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV TFA preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV TFA has analgesic effects on animal models of inflammatory and neuropathic pain.
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NaV1.7 inhibitor-1
0 ImagesNaV1.7 inhibitor-1 is an efficacious voltage-gated sodium channel (NaV) 1.7 inhibitor with an IC50 of 0.6 nM for hNaV1.7, exhibits 80-fold selectivity versus hNaV1.5.
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PF-05186462
0 ImagesPF-05186462 is a potent and selective inhibitor of human Nav1.7 voltage-dependent sodium channel, with an IC50 of 21 nM. PF-05186462 shows significant selectivity for Nav1.7 versus other sodium channels (Nav 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, and 1.8). PF-05186462 can be used for the research of acute or chronic pain.
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PF-05198007
0 ImagesPF-05198007 is a potent, orally active and selective arylsulfonamide Nav1.7 inhibitor. PF-05198007 is a compound with a similar pharmacodynamic profile to PF-05089771.
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E0199
0 ImagesE0199 is a novel potent dual-target KV7/NaV modulator that activates the KV7 channel (KV7.2/7.3 (EC50 = 12.78 nM), KV7.2 (EC50 = 0.50 μM), and KV7.5 (EC50 = 27.14 nM) channels) while simultaneously blocks the NaV1.7 (IC50 = 0.52 μM), NaV1.8 (IC50 = 0.24 μM), and NaV1.9 (IC50 = 0.16 μM) channels. E0199 shows a potent analgesic effect without affecting heart and skeletal muscle ion channels critically in a chronic constriction injury (CCI) mouse model. E0199 can be used for Neuropathic pain (NP) research.
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Aneratrigine
0 ImagesAneratrigine is a selective Nav1.7 inhibitor with an IC50 of 19 nM. Aneratrigine is applicable for pain-related research.
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GpTx-1 TFA
0 ImagesCat. No.: HY-P1681APurity: 99.56%GpTx-1 TFA is a peptide-based NaV1.7 sodium channel antagonist isolated from the venom of the Chilean spider Grammostola porter. GpTx-1 TFA demonstrates potent inhibitory activity against the NaV1.7 channel with an IC50 value of 10 nM, while exhibiting excellent selectivity for NaV1.4 (IC50 = 0.301 μM) and NaV1.5 (IC50 = 4.20 μM), showing >20-fold and >950-fold selectivity respectively.
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ProTx-I
0 ImagesProTx-I is a toxin derived from Thrixopelma pruriens and a peptide inhibitor targeting TTX-resistant sodium channels. ProTx-I interacts with voltage sensors of multiple domains such as NaV1.7, reduces neuronal excitability through allosteric modulation of channel gating and alteration of voltage dependence. The IC50 values of ProTx-I against human NaV1.7, NaV1.2, NaV1.6, and NaV1.5 are 95 nM, 104 nM, 21 nM, and 358 nM, respectively; ProTx-I also potently inhibits Ba2+ currents of hCav3.1, while its inhibitory potency against hCav3.2 is approximately 160-fold lower. ProTx-I is applicable to the research of chronic pain.
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Nav1.7-IN-19
0 ImagesNav1.7-IN-19 is a potent, selective and orally active Nav1.7 inhibitor with an IC50 of 0.49 μM. Nav1.7-IN-19 shows high selectivity for Nav1.7, with selectivities of 312-fold and 662-fold against Nav1.1 and Nav1.5 in the inactivated state. Nav1.7-IN-19 exhibits weak inhibition on hERG potassium channels. Nav1.7-IN-19 exhibits analgesic effect and can be used for the research of neurological disease.
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(Rac)-AMG8379
0 ImagesSynonyms: (Rac)-AMG8380(Rac)-AMG8379 ((Rac)-AMG8380) is a racemate of AMG8379. AMG8379 is a potent, orally active and selective sulfonamide antagonist of NaV1.7, with IC50s of 8.5 and 18.6 nM for hNaV1.7 and mNaV1.7, respectively .
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(R)-Funapide
0 ImagesSynonyms: (R)-TV 45070; (R)-XEN402(R)-Funapide ((R)-TV 45070) is the less active R-enantiomer of Funapide. Funapide is a potent inhibitor of the sodium channel Nav1.7, Nav1.8 and other Nav channels expressed in the peripheral nervous system. Fornabil is an orally effective analgesic agent.
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4',7-Di-O-methylnaringenin
0 ImagesSynonyms: (-)-Naringenin 4',7-dimethyl Ether; (-)-NRG-DM4',7-Di-O-methylnaringenin ((−)-NRG-DM) is a flavonoid found in Renealmia alpinia. (−)-NRG-DM inhibits Nav1.7, Nav1.8 and Kv2.1 channels and has analgesic activity. Intraperitoneal administration of (−)-NRG-DM dose-dependently attenuated pain in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model[2].
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Sodium Channel inhibitor 1
0 ImagesSodium Channel inhibitor 1 is a state-dependent voltage-gated NaV1.7 inhibitor with an IC50 of 0.087 μM. Sodium Channel inhibitor 1 can be used for research of pain.
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Nav1.7-IN-2
0 ImagesNav1.7-IN-2 is an inhibitor of voltage-gated sodium channels (Nav), in particular Nav 1.7, with IC50 of 80 nM.
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GX-936
0 ImagesCat. No.: HY-123414CAS No.: 1235406-09-3Synonyms: PF-05196233GX-936 (PF-05196233) is a selective Nav1.7 inhibitor. GX-936 binds to the activated VSD4, forms a bidentate salt bridge with the R4 of the S4 helix, traps VSD4 in the activated state, and prevents the channel from recovering from the inactivated state. GX-936 can be used in studies related to pain.
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Nav1.7-IN-6
0 ImagesCat. No.: HY-102998CAS No.: 1788066-71-6Nav1.7-IN-6 (example 346) is a Nav1.7 selective inhibitor, which is extracted from patent WO2015078374A1.
