Discovery of Novel 2,3-Dihydro-1<i>H</i>-indene-5-sulfonamide NLRP3 Inflammasome Inhibitors Targeting Colon as a Potential Therapy for Colitis

Sun, Simin; Li, Zhuoyue; Huang, Chao; Liu, Jinyu; Yu, Qixin; Jiang, Xiaolin; Yue, Kairui; Zhao, Jianchun; Xu, Tongqiang; Liu, Yankai; Li, Xiaoyang; Qin, Chong; Jiang, Yuqi

doi:10.1021/acs.jmedchem.3c01511

J. Med. Chem.

2023

DOI: 10.1021/acs.jmedchem.3c01511

|View full text |Cite

Discovery of Novel 2,3-Dihydro-1H-indene-5-sulfonamide NLRP3 Inflammasome Inhibitors Targeting Colon as a Potential Therapy for Colitis

Simin Sun,

Zhuoyue Li,

Chao Huang

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article4

Relationship

Self Cite0

Independent4

Authors

Journals

Cited by 4 publications

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors

Huang,

Liu,

Chen

et al. 2024

Bioorganic Chemistry

View full text Add to dashboard Cite

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors

Huang,

Liu,

Chen

et al. 2024

Bioorganic Chemistry

View full text Add to dashboard Cite

Design, synthesis and biological evaluation of novel diphenylamine analogues as NLRP3 inflammasome inhibitors

Kang,

Sun,

Wang

et al. 2024

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Design, Synthesis, and Bioevaluation of Novel NLRP3 Inhibitor with IBD Immunotherapy from the Virtual Screen

Zhang,

Wu,

Yin

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

NLRP3, a crucial member of the NLRP family, plays a pivotal role in immune regulation and inflammatory modulation. Here, we report a potent and specific NLRP3 inhibitor Z48 obtained though docking-based virtual screening and structure−activity relationship studies with an IC 50 of 0.26 μM in THP-1 cells and 0.21 μM in mouse bone marrow-derived macrophages. Mechanistic studies indicated that Z48 could bind directly to the NLRP3 protein (K D = 1.05 μM), effectively blocking the assembly and activation of the NLRP3 inflammasome, consequently manifesting anti-inflammatory properties. Crucially, with acceptable mouse pharmacokinetic profiles, Z48 demonstrated notable therapeutic efficacy in a mouse model of DSSinduced ulcerative colitis, while displaying no significant therapeutic impact on NLRP3 KO mice. In conclusion, this study provided a promising NLRP3 inflammasome inhibitor with novel molecular scaffold, poised for further development as a therapeutic candidate in the treatment of inflammatory bowel disease.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Discovery of Novel 2,3-Dihydro-1H-indene-5-sulfonamide NLRP3 Inflammasome Inhibitors Targeting Colon as a Potential Therapy for Colitis

Cited by 4 publications

References 53 publications

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors

Design, synthesis and biological evaluation of novel diphenylamine analogues as NLRP3 inflammasome inhibitors

Design, Synthesis, and Bioevaluation of Novel NLRP3 Inhibitor with IBD Immunotherapy from the Virtual Screen

Contact Info

Product

Resources

About