Table 3.

TRPV3 antagonists.

Entry	Name	Structure	Activate	Inhibit	IC50 for TRPV3	Description/Use	Reference(s)
Natural compounds
1	Citrusinine II		—	TRPV3	12.43 μM	Citrusinine II can selectively inhibit TRPV3 and reduce itchy behavior by interacting with Y564 in the TRPV3 helix.	[104]
2	Osthole		—	TRPV1 TRPV3	37.0 ± 1.9 μM	Cusson, isolated from Cnidium monnieri (L.), is used as an antipruritic herbal medicine.	[105,141]
3	Isochlorogenic acid A		—	TRPV3	2.7 ± 1.3 μM	A TRPV3 specific inhibitor that can significantly reverse ear swelling in dermatitis and chronic pruritus.	[107]
4	Isochlorogenic acid B		—	TRPV3	0.9 ± 0.3 μM	A TRPV3 specific inhibitor that can significantly reverse ear swelling in dermatitis and chronic pruritus.	[107]
5	Forsythoside B		—	TRPV3	6.7 ± 0.7 μM	A TRPV3 inhibitor that can significantly reduce acute pruritus.	[108]
6	Monanchomycalin B		—	TRPV1 TRPV2 TRPV3	3.25 μM	A TRPV inhibitor that is isolated from the marine sponge Monanchora pulchra.	[112]
7	Verbascoside		—	TRPV3	14.1 ± 3.3 μM	A TRPV3 inhibitor that can effectively relieve atopic dermatitis when applied topically.	[109]
8	Pulchranin A		—	TRPV1 TRPV3 TRPA1	71.8 ± 9.4 μM	A moderately potent TRPV1 inhibitor and a minimally potent TRPV3 and TRPA1 inhibitor that is isolated from marine sponge Monanchora pulchra.	[110,111]
9	Pulchranin B		—	TRPV1 TRPV3 TRPA1	117.9 ± 11.8 μM	A moderately potent TRPV1 inhibitor and a minimally potent TRPV3 and TRPA1 inhibitor that is isolated from marine sponge Monanchora pulchra.	[110]
10	Pulchranin C		—	TRPV1 TRPV3 TRPA1	>200 μM	A moderate potent TRPV1 inhibitor and a minimally potent TRPV3 and TRPA1 inhibitor that is isolated from marine sponge Monanchora pulchra.	[110]
Synthetic compounds
11	Ruthenium Red		—	TRP(S)	NA	Broad-spectrum, non-selective, cationic channel blockers.	[113]
12	2,2-diphenyltetrahydro-furan (DPTHF)		—	TRPV1 TRPV2 TRPV3	6–10 μM	2-APB structural analogue.	[115]
13	PC5		—	TRPV3	2.63 ± 0.28 μM	A TRPV3 inhibitor that is obtained by virtual protein structure screening and lead compound structure optimization.	[116]
14	7C		—	TRPV3	1.05 μM	A TRPV3 inhibitor that is obtained by the bioelectron isoarrangement principle.	[117]
15	Bupivacaine		—	TRPV3	0.17 ± 0.04 mM	A TRPV3 inhibitor that can be used as local anesthetics by extracellular interactions of their charged forms with the TRPV3 channel pore.	[118]
16	Mepivacaine		—	TRPV3	1.4 ± 0.3 mM	A TRPV3 inhibitor that can be used as local anesthetics by extracellular interactions of their charged forms with the TRPV3 channel pore.	[118]
17	Lidocaine		—	TRPV3	2.5 ± 0.5 mM	A TRPV3 inhibitor that can be used as local anesthetics by extracellular interactions of their charged forms with the TRPV3 channel pore.	[118]
18	Ropivacaine		—	TRPV3	0.28 ± 0.04 mM	A TRPV3 inhibitor that can be used as local anesthetics by extracellular interactions of their charged forms with the TRPV3 channel pore.	[118]
19	Dyclonine		—	TRPV3	3.2 μM	A TRPV3 inhibitor that can ameliorate the hyperactivity caused by itch/scratching behaviors.	[119]
20	Example #64 (WO 2006/122156)		—	TRPV3	0.2–1 μM	A TRPV3 inhibitor discovered by Hydra Biosciences that can reduce heat sensitivity after carrageenan injection in burns or hind paws.	[121]
21	DCP-THQ (WO 2007/056124)		—	TRPV3	117 nM	A TRPV3 inhibitor discovered by Hydra Biosciences.	[123]
22	Example #19 (US 2010/0292554A1)		—	TRPV3	200–1000 nM	A TRPV3 inhibitor discovered by Glenmark.	[124]
23	Example #58 (US 2009/0286811A1)		—	TRPV3	< 500 nM	A TRPV3 inhibitor discovered by Glenmark.	[125]
24	Example #58 (WO 2009/130560)		—	TRPV3	<250 nM	A TRPV3 inhibitor discovered by Glenmark.	[126]
25	Example #23 (WO 2010/055384)		—	TRPV3	<50 nM	A TRPV3 inhibitor discovered by Glenmark.	[127]
26	Example #7 (US2010/0152192)		—	TRPV3	<100 nM	A TRPV3 inhibitor discovered by Glenmark.	[128]
27	Example #37 (US2010/0152192)		—	TRPV3	<100 nM	A TRPV3 inhibitor discovered by Glenmark.	[128]
28	Example #83 (WO2010/073128)		—	TRPV3	<50 nM	A TRPV3 inhibitor discovered by Glenmark.	[129]
29	74a		—	TRPV3	0.38 μM	A high potent TRPV3 inhibitor discovered by Glenmark that can be effective in rat neuropathic pain model.	[130]
Endogenous substance
30	17R-RvD1		—	TRPV3	0.4 μM	An endogenous TRPV3 inhibitor of endogenous lipid metabolites.	[142]
31	Isopentenyl pyrophosphate (IPP)		—	TRPV3 TRPA1	0.24 μM	An endogenous TRPA1 and TRPV3 inhibitor for topical analgesia.	[143]