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. Author manuscript; available in PMC: 2024 Jul 26.
Published in final edited form as: Expert Opin Ther Pat. 2023 Jul 26;33(6):455–470. doi: 10.1080/13543776.2023.2239502

Table 2.

Representative NLRP3 inhibitors are in preclinical or early clinical stages reported from recently filed patents and articles.

Inhibitor MOAs IC50 (IL-1β release)# Preclinical disease models* Development Stage
CY-09
graphic file with name nihms-1919208-t0011.jpg 		Binds to Walker A site in NACHT domain
Inhibits ATPase activity		 6 μM T2DM, diabetic retinopathy, diabetic liver injury, NAFLD, peritonitis, Muckle-Wells syndrome, epilepsy Preclinical
Tranilast
graphic file with name nihms-1919208-t0012.jpg 		Disrupts NLRP3-NLRP3 oligomerization through NACHT domain binding <25 μM T2DM, NASH, colitis, peritonitis, Muckle-Wells syndrome, atherosclerosis Phase II clinical trials to treat cryopin associated periodic syndrome (CAPS) (NCT03923140)
Phase IV trial for percutaneous coronary intervention (NCT05130892)
Oridonin
graphic file with name nihms-1919208-t0013.jpg 		Covalently binds to Cys279 of NACHT domain and reduces NLRP3-NEK7 interaction <0.5 μM T2DM, liver fibrosis, IBD, peritonitis, hearing loss, pleurisy Phase IV trial for percutaneous coronary intervention (NCT05130892)
RRx-001
graphic file with name nihms-1919208-t0014.jpg 		Covalently binds to Cys409 of NACHT domain and reduces NLRP3-NEK7 interaction 117 nM EAE, DSS colitis Phase III clinical trials adjuvant treatment of small cell lung cancer with platinum (NCT03699956)
Bay-11-7082
graphic file with name nihms-1919208-t0015.jpg 		Inhibits ATPase activity
Unknown binding site		 ~3 μM T2DM, IBD, psoriasis, lupus nephritis Preclinical
BOT-4-one
graphic file with name nihms-1919208-t0016.jpg 		Inhibits ATPase activity
Unknown binding site		 1.28 μM (LPS/ATP)
0.67 μM (LPS/nigericin)		 Peritonitis, dermatitis, psoriasis, arthritis Preclinical
OLT1177 (Dapansutrile)
graphic file with name nihms-1919208-t0017.jpg 		Inhibits ATPase activity
Unknown binding site		 ND AD, EAE, colitis, arthritis Phase II clinical trials to treat acute gouty arthritis (EudraCT 2016-000943-14)
INF39
graphic file with name nihms-1919208-t0018.jpg 		Covalent inhibitor of ATPase activity
Unknown binding site		 ~10 μM IBD, colitis, pancreatitis Preclinical
JC-171
graphic file with name nihms-1919208-t0019.jpg 		Reduces NLRP3-ASC interaction
Unknown binding site		 8.45 μM EAE Preclinical
VTX2735 Peripherally restricted NLRP3 inhibitor 4 nM N/A Phase II clinical trial to treat cryopyrin associated periodic syndrome (NTC05812781)
Emlenoflast (Inzomelid; MCC7840; IZD174)
graphic file with name nihms-1919208-t0020.jpg 		NLRP3 inflammasome inhibitor
Unknown binding site		 4.7 nM N/A Phase I clinical trials for safety and tolerability (NCT04015076)
Phase IIb clinical trials to treat cryopyrin associated periodic syndrome (CAPS) (EudraCT2020-000489-40)
Selnoflast (RG6418; RO7486967)
graphic file with name nihms-1919208-t0021.jpg 		NLRP3 inflammasome inhibitor
Unknown binding site		 ≤ 1 μM (THP-1 cells) N/A Phase Ib clinical trials for safety and tolerability in ulcerative colitis patients (BP43099)
Phase Ib clinical trials for safety and tolerability in patients with early idiopathic Parkinson’s disease (BP43176, CPMS 50823, IRAS 307220)
#

IC50 values for IL-1β release inhibition in murine macrophage cells.

*

Abbreviations: AD: Alzheimer’s disease, PD: Parkinson’s disease, EAE: Experimental autoimmune encephalomyelitis, EAT: Experimental autoimmune thyroiditis, T2DM: Type 2 diabetes mellitus, NAFLD: Non-alcoholic fatty liver disease, NASH: Non-alcoholic steatohepatitis, IBD: Irritable bowel disease, DSS: Dextran sulfate sodium. ND: not determined.