Table 1.

Selected small molecule inhibitors, drugs, and protein scaffolds that interfere with IL-23 signaling cascade.

Inhibitor	Target	Clinical Phase	Disease/Model	Route	Reference
IL-23R peptide antagonist	IL-23R	Preclinical	rIL-23-induced skin inflammation model, anti-CD40 systemic inflammation, CIA	i.p.*	[63]
IL-23 Alphabodies	IL-23	Preclinical	rIL-23-induced skin inflammation model	i.d., i.p.	[64]
Tofacitinib	Jak1, Jak3, Jak2	Approved	Rheumatoid and psoriasic arthritis, ulcerative colitis	oral	[78]
		Phase 3	Juvenile arthritis, systemic lupus erythematosus	oral
		Phase 2	Atopic dermatitis	topical
Ruxolitinib	Jak1, Jak2	Phase 2	Rheumatoid arthritis	oral	[78]
		Phase 2	Atopic dermatitis	topical
Baricitinib	Jak1, Jak2	Approved	Rheumatoid arthritis	oral	[78]
		Phase 2	Psoriasis, systemic lupus erythematosus	oral
		Phase 3	Atopic dermatitis	topical
BMS-986165	Tyk2	Phase 2	Psoriasis, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, systemic lupus erythematosus	oral	[80]
Brepocitinib (PF-06700841)	Tyk2, Jak1	Phase 2	Psoriasis, Crohn’s disease, ulcerative colitis	oral	[81]
Baicalin	STAT3/SOCS3	Preclinical	EAE model	i.p.	[98]
Fasudil	ROCK	Preclinical	EAE model	oral, i.p.	[116,117]
WAR5 compound	ROCK	Preclinical	EAE model	i.p.	[118]
Statins	ROCK	Preclinical	EAE model	i.p.	[119]
KD025	ROCK	Phase 2	Psoriasis vulgaris	oral	[120]
Fingolimod (FTY720)	S1PR1	Approved	Multiple sclerosis	oral	[127]
		Preclinical	IMQ-induced skin inflammation model	i.p.	[128]
Natalizumab	VLA4	Approved	Multiple sclerosis, Crohn’s disease	i.v.	[129]
TEPP-46	PKM2	Preclinical	EAE model	i.p.	[132]
CH-223191	AhR inhibitor	Preclinical	IL-23-induced skin inflammation model	i.p.	[139]
FICZ	AhR agonist	Preclinical	IMQ-induced skin inflammation model	i.p	[141]
Nitric oxide carriers	AhR	Preclinical	EAE model	oral	[147]
Digoxin	RORγt	Preclinical	EAE model	i.p.	[155]
SR1001	RORαt, RORγt	Preclinical	EAE model	i.p.	[156]
TMP778	RORγt	Preclinical	EAE model	s.c.	[157]
GSK805	RORγt	Preclinical	EAE model	s.c.	[157]
JNJ-54271074	RORγt	Preclinical	CIA and IL-23-induced skin inflammation models	oral	[158]
JPH203	LAT1	Preclinical	IMQ-induced skin inflammation model	i.p.	[140]
Rapamycin	mTOR	Preclinical	IMQ-induced skin inflammation model	i.p.	[140]

Abbreviations: rIL-23, recombinant IL-23; i.p, intraperitoneal; i.d., intradermal: i.v., intravenous; s.c. subcutaneous.