MK-5661 is an orally potent Na V 1.8 voltage-gated sodium channel inhibitor with an EC 50 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 [1].
In Vivo, MK-5661 (0.1-10 mg/kg; p.o.; single dose) dose-dependently inhibits capsaicin-induced nocifensive behavior in humanized rats[1]. MK-5661 (0.2-2 mg/kg; p.o.; single dose) significantly attenuates capsaicin-induced dermal flare area in rhesus macaques[1].
In Vitro, MK-5661 potently modulates human NaV1.8 channels stably expressed in HEK 293 cells with an EC50 of 4.3 nM and a VLE of 6.5[1]. MK-5661 is highly selective for human NaV1.8 channels, with IC50 values greater than 30 μM against human NaV1.2, NaV1.4, NaV1.5, NaV1.6, and NaV1.7 channels stably expressed in HEK-293 cells[1].
References:
[1]. Bungard CJ, et al. Discovery of MK-5661, a Once-Daily Oral Na V 1.8 Inhibitor for the Treatment of Pain. ACS Med Chem Lett. 2026;17(5):1189-1194. Published 2026 Apr 24.
In Vivo, MK-5661 (0.1-10 mg/kg; p.o.; single dose) dose-dependently inhibits capsaicin-induced nocifensive behavior in humanized rats[1]. MK-5661 (0.2-2 mg/kg; p.o.; single dose) significantly attenuates capsaicin-induced dermal flare area in rhesus macaques[1].
In Vitro, MK-5661 potently modulates human NaV1.8 channels stably expressed in HEK 293 cells with an EC50 of 4.3 nM and a VLE of 6.5[1]. MK-5661 is highly selective for human NaV1.8 channels, with IC50 values greater than 30 μM against human NaV1.2, NaV1.4, NaV1.5, NaV1.6, and NaV1.7 channels stably expressed in HEK-293 cells[1].
References:
[1]. Bungard CJ, et al. Discovery of MK-5661, a Once-Daily Oral Na V 1.8 Inhibitor for the Treatment of Pain. ACS Med Chem Lett. 2026;17(5):1189-1194. Published 2026 Apr 24.