Imperial College London

DrRaviSingh

Faculty of Natural SciencesDepartment of Chemistry

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 5821ravi.singh

 
 
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Location

 

301Molecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

3 results found

Kennedy C, Goya Grocin A, Kovacic T, Singh R, Tate E, Ward J, Shenoy Aet al., 2021, A probe for NLRP3 inflammasome inhibitor MCC950 identifies carbonic anhydrase 2 as a novel target, ACS Chemical Biology, Vol: 16, Pages: 982-990, ISSN: 1554-8929

Inhibition of inflammasome and pyroptotic pathways are promising strategies for clinical treatment of autoimmune and inflammatory disorders. MCC950, a potent inhibitor of the NLR-family inflammasome pyrin domain-containing 3 (NLRP3) protein, has shown encouraging results in animal models for a range of conditions; however, until now, no off-targets have been identified. Herein, we report the design, synthesis, and application of a novel photoaffinity alkyne-tagged probe for MCC950 (IMP2070) which shows direct engagement with NLRP3 and inhibition of inflammasome activation in macrophages. Affinity-based chemical proteomics in live macrophages identified several potential off-targets, including carbonic anhydrase 2 (CA2) as a specific target of IMP2070, and independent cellular thermal proteomic profiling revealed stabilization of CA2 by MCC950. MCC950 displayed noncompetitive inhibition of CA2 activity, confirming carbonic anhydrase as an off-target class for this compound. These data highlight potential biological mechanisms through which MCC950 and derivatives may exhibit off-target effects in preclinical or clinical studies.

Journal article

Singh R, Li Z, Foster R, Mistry Net al., 2021, A Classroom-Based Activity to Teach Students How to Apply Organic Chemistry Theory to Design Experiments, JOURNAL OF CHEMICAL EDUCATION, Vol: 98, Pages: 515-520, ISSN: 0021-9584

Journal article

Mistry N, Singh R, Ridley J, 2020, A Web-Based Stereochemistry Tool to Improve Students' Ability to Draw Newman Projections and Chair Conformations and Assign R/S Labels, JOURNAL OF CHEMICAL EDUCATION, Vol: 97, Pages: 1157-1161, ISSN: 0021-9584

Journal article

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