Inhibition of NaV1.7: the possibility of ideal analgesics

. 2022 Aug 1;13(8):895–920. doi: 10.1039/d2md00081d


	GDC-0276 (38)⁷⁸	39: Amgen⁹⁹	40: Bristol-Myers Squibb⁹⁴	41: Xenon/Genentech¹⁰⁰	GNE-131 (42)¹⁰¹
hNa_V1.1 IC₅₀	10.6 nM^d^,^g	8500 nM^c^,^h	—	6 nM^d^,^g	45 nM^d^,^g
hNa_V1.5 IC₅₀	51 nM^d^,^g	11 900 nM^c^,^h	19 000 nM^g^,^k	50 nM^d^,^g	110 nM^d^,^g
hNa_V1.7 IC₅₀	0.4 nM^d^,^g	51 nM^c^,^h	8 nM^c^,^l	0.6 nM^d^,^g	3 nM^d^,^g
Mouse Na_V1.7 IC₅₀	—	115 nM, 270 nMⁱ	35 nM^c^,^l, 11 nM^c^,^l^,^m	2.2 nM^d^,^g	—
Mouse PPB^b	99.98%	98.6%	99.8%, 96.5%ⁿ	99.9%	99.9%
Na_V1.7 coverage in plasma@efficacious dosage^a	1-Fold@in vivo EC₅₀ (IEM mouse)	36-Fold@300 mg kg⁻¹ (15-fold@300 mg kg⁻¹^j) (mouse histamine)	8.7-Fold@30 mg kg⁻¹ IP^o	5-Fold@0.30 mg kg⁻¹ (IEM mouse)	0.17-Fold@in vivo EC₅₀ (IEM mouse)
			3.4-Fold@30 mg kg⁻¹ IP (mouse formalin)	23-Fold@10 mg kg⁻¹ (mouse formalin)
			3.6-Fold@30 mg kg⁻¹ IP (mouse CFA)
			3.9-Fold@30 mg kg⁻¹ IP (mouse CCI)