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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GNE-616
0 ImagesCat. No.: HY-126291CAS No.: 2349371-81-7GNE-616 is a highly potent, metabolically stable, orally bioavailable, and subtype selective Nav1.7 inhibitor (Ki of 0.79 nM and Kd of 0.38 nM for hNav1.7) for the treatment of chronic pain. GNE-616 shows >1000 nM Kd and >2500-fold selectivity over hNav1.1, hNav1.3, hNav1.4, and hNav1.5. Selectivity over hNav1.2 and hNav1.6 is more modest at 31- and 73-fold, respectively.
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AMG8379
0 ImagesCat. No.: HY-108425CAS No.: 1642112-31-9AMG8379 is a potent, orally active and selective sulfonamide antagonist of the voltage-gated sodium channel NaV1.7, with IC50s of 8.5 and 18.6 nM for hNaV1.7 and mNaV1.7, respectively. AMG8379 potently and reversibly blocks endogenous Tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglia (DRG) neurons with an IC50 of 3.1 nM.
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AMG8380
0 ImagesCat. No.: HY-108425ACAS No.: 1642112-32-0AMG8380, an orally active and less active enantiomer of AMG8379, can serves as a negative control. AMG8380 inhibits human and mouse voltage-gated sodium channel NaV1.7 with IC50s of 0.907 and 0.387 μM, respectively. AMG8380 blocks Tetrodotoxin (TTX)-sensitive native channels with an IC50 of 2560 nM.
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PF-06456384
0 ImagesCat. No.: HY-118952CAS No.: 1834610-73-9PF-06456384 is a highly potent and selective NaV1.7 inhibitor with an IC50 of 0.01 nM. PF-06456384 has the potential for formalin pain model research.
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Pterinotoxin-1
0 ImagesCat. No.: HY-P5943Pterinotoxin-1 is a sodium channel inhibitor peptide toxin.
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Nav1.7-IN-22
0 ImagesCat. No.: HY-182831CAS No.: 1432512-70-3Nav1.7-IN-22 (P58 13-2) is a selective inhibitor of voltage-gated sodium channel Nav1.7. Nav1.7-IN-22 inhibits abnormal electrical signal generation and conduction in sensory neurons by blocking Nav1.7 channel activity. Nav1.7-IN-22 can be used for the study of pain.
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Pterinotoxin-2
0 ImagesCat. No.: HY-P5942Pterinotoxin-2 is a sodium channel inhibitor peptide toxin.
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GpTx-1
0 ImagesCat. No.: HY-P1681CAS No.: 1661050-12-9GpTx-1 is a peptide-based NaV1.7 sodium channel antagonist isolated from the venom of the Chilean spider Grammostola porter. GpTx-1 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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Aneratrigine hydrochloride
0 ImagesCat. No.: HY-156596ACAS No.: 2097163-75-0Aneratrigine hydrochloride is a selective Nav1.7 inhibitor with an IC50 of 19 nM. Aneratrigine hydrochloride is applicable for pain-related research.
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Hainantoxin-III
0 ImagesCat. No.: HY-P5180CAS No.: 1809149-40-3Jingzhaotoxin-V is a peptide that inhibits potassium currents in Xenopus laevis oocytes with an IC50 value of 604.2 nM. Jingzhaotoxin-V also inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons with IC50 values of 27.6 and 30.2 nM, respectively.
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Nav1.7-IN-23
0 ImagesCat. No.: HY-189066CAS No.: 3138159-82-4Nav1.7-IN-23 is an orally active, selective NaV1.7 inhibitor. Nav1.7-IN-23 exhibits electrophysiological regulatory effects in mouse dorsal root ganglion neurons. Nav1.7-IN-23 can be used for the research of acute pain, chronic inflammatory pain and neuropathic pain.
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PF-06526290
0 ImagesCat. No.: HY-126007PF-06526290 is a voltage-gated sodium (Nav) channel modulator with dual activity of enhancing and inhibiting Nav channel conduction. PF-06526290 slows inactivation by binding to the resting state of Nav channels, and exerts inactivation state-dependent inhibition after prolonged depolarization by acting on the voltage sensor of the fourth homologous domain 4 (D4 VSD). PF-06526290 can be used in research on neurological disorders such as epilepsy and autism.
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ProTx-III
0 ImagesCat. No.: HY-P5153CAS No.: 1808297-63-3Synonyms: μ-TRTX-Tp1aProTx-III is a selective and potent inhibitor of voltage-gated sodium channel Nav1.7, with an IC50 of 2.1 nM. ProTx-III is a spider venom peptide isolated from the venom of the Peruvian green velvet tarantella. ProTx-III has a typical inhibitor cystine knot motif (ICK). ProTx-III is able to reverse the pain response. ProTx-III can be used to study diseases such as chronic pain, epilepsy, and arrhythmia.
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Nav1.7-IN-8
0 ImagesCat. No.: HY-141547CAS No.: 1432913-44-4Nav1.7-IN-8 is a potent blockage of NaV1.7 with high selectivity for the inhibition of NaV1.7 over the subtypes hNaV1.1 and hNaV1.5. Nav1.7-IN-8 inhibits CYP2C9 and CYP3A4 with an IC50 of 0.17 μM and 0.077 μM, respectively. Nav1.7-IN-8 displays significant analgesic effects in rodent models of acute and inflammatory pain.
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Huwentoxin-IV
0 ImagesCat. No.: HY-P1220CAS No.: 526224-73-7Huwentoxin-IV 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 preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV has analgesic effects on animal models of inflammatory and neuropathic pain.
