Na_v1.8 Inhibitor

A-803467 is a potent and selective tetrodotoxin-resistant Na_v1.8 sodium channel blocker (IC₅₀=8 nM). A-803467 has shown significant anti-nociception in neuropathic and inflammatory pain models. A-803467 enhances the chemosensitivity of conventional anticancer agents through interaction with the ATP-binding cassette subfamily G member 2 (ABCG2) transporter.

DSP-2230 is the orally active inhibitor for voltage-gated sodium channel that inhibits Nav1.7-, Nav1.8-, and Nav1.9-derived sodium currents with IC₅₀s of 7.1 μM, 11.4 μM and 6.7 μM, respectively. DSP-2230 can be used to improve neuropathic pain.

ICA-121431 is a nanomolar potent and broad-spectrum voltage-gated sodium channel (Na_v) blocker, shows equipotent selectivity for human Na_v1.1 and Na_v1.3 subtypes with IC₅₀ values of 13 nM and 23 nM, respectively. ICA-121431 shows less potent inhibition of Na_v1.2 (IC₅₀=240 nM) and 1,000 fold selectivity against Na_v1.4, Na_v1.6, and the TTX-resistant human Na_v1.5 and Na_v1.8 channels (IC₅₀s >10 μM).

PF-06456384 trihydrochloride is an extremely potent and selective Na_v1.7 sodium channel blocker (IC₅₀: 0.01 nM for hNaV1.7; 75 nM for rNaV1.7; <0.1 nM for mNaV1.7). PF-06456384 trihydrochloride shows no significant analgesic efficacy in the mouse Formalin pain model.

TC-N 1752 is a potent and orally active inhibitor of Nav1.7, with IC₅₀s of 0.17 μM, 0.3 μM, 0.4 μM, 1.1 μM and 2.2 μM at hNav1.7, hNav1.3, hNav1.4, hNaV1.5 and rNav1.8, respectively. TC-N 1752 also inhibits tetrodotoxin-sensitive sodium channels. TC-N 1752 shows analgesic efficacy in the Formalin model of pain.

Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

MK-5661 is an orally potent Na_V1.8 voltage-gated sodium channel inhibitor with an EC₅₀ of 4.3 nM. MK-5661 selectively inhibits peripheral nociceptive signaling mediators. MK-5661 reduces capsaicin-induced spontaneous nociceptive behaviors in humanized rats and attenuates capsaicin-induced skin flushing responses in rhesus monkeys. MK-5661 is applicable for pain-related research.

Nav1.8-IN-19 (Compound 70) is a Nav1.8 inhibitor.

LTGO-33 is a potent and selective voltage-gated sodium channel NaV1.8 inhibitor. LTGO-33 inhibits NaV1.8 in the nM potency range and exhibits over 600-fold selectivity against human NaV1.1-NaV1.7 and NaV1.9. LTGO-33 exhibits state-independent inhibition with similar potencies on channels in the closed and inactivated conformations. LTGO-33 inhibits native TTX-R NaV1.8 currents in non-human primate and human DRG neurons, where it reduces action potential firing. LTGO-33 can be used for pain disorders research.

A-887826 is a potent, selective, oral bioavailable and voltage-dependent Na(v)1.8 sodium channel blocker with an IC₅₀ of 11 nM . A-887826 attenuates neuropathic tactile allodynia in vivo.

Sodium Channel inhibitor 6 (compound I) is a selective Na_v1.8 inhibitor that can be used in the study of neuropathic pain.

Funapide (TV 45070; XEN402) is an orally active inhibitor of voltage-gated sodium channels (VGSC) in the peripheral nervous system with IC₅₀ values ??of 84 nM and 54 nM for Nav1.5 and Nav1.7, respectively. Funapide has analgesic effects.

Cyfluthrin is a type II pyrethroid and has effects on various insects. Cyfluthrin is a modulator of Nav_1.8 sodium channels by repetitive stimulation. Cyfluthrin can be applied in agriculture,veterinary, insecticide,pyrethroid and stored product.

PF-06305591 is a potent and highly selective voltage gated sodium channel NaV1.8 blocker, with an IC₅₀ of 15 nM. An excellent preclinical in vitro ADME and safety profile.

VX-150 is an orally active, highly selective Na_V1.8 inhibitor. VX-150 has the potential for various pain indications research.

PF-01247324 is a selective and orally bioavailable Na_v1.8 channel blocker with an IC₅₀ of 196 nM for recombinant human Na_v1.8 channel.

3'-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.

Nav1.8-IN-2 (compound 35A) is a Nav1.8 voltage-gated sodium ion inhibitor with an IC₅₀ of 0.4 nM (HEK 293 cells). Nav1.8-IN-2 inhibits the activity of Nav1.8 voltage-gated sodium ion channels, mediates sodium ion influx in excitable cells, and is associated with the initiation and conduction of action potentials. Nav1.8-IN-2 can be used for research related to pain, cough, itching, etc.

ABBV-318 is a potent Nav1.7/ Nav1.8 blocker, with IC₅₀s of 2.8 μM and 3.8 μM for hNav1.7 and hNav1.8, respectively. ABBV-318 can be used for the research of pain.

E0199 is a novel potent dual-target K_V7/Na_V modulator that activates the K_V7 channel (K_V7.2/7.3 (EC₅₀ = 12.78 nM), K_V7.2 (EC₅₀ = 0.50 μM), and K_V7.5 (EC₅₀ = 27.14 nM) channels) while simultaneously blocks the Na_V1.7 (IC₅₀ = 0.52 μM), Na_V1.8 (IC₅₀ = 0.24 μM), and Na_V1.9 (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.