MCC950   Click here for help

GtoPdb Ligand ID: 8228

Synonyms: CP-456,773 | CP-456773 | CRID3 | MCC-950
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: MCC950 has been reported as a potent, selective and direct inhibitor of the NLRP3 inflammasome [4-5]. The compound binds directly at a motif within the NLRP3 protein's NACHT domain [2] and blocks its activation and inflammasome formation which ultimately reduces cleavage of IL-1β and IL-18 from their latent forms. It offers a useful tool for examination of NLRP3 biology and its potential for therapeutic intervention. MCC950 has demonstrated anti-inflammatory actions in numerous in vivo models of human diseases [3-4] and has been proposed as a therapeutic option for the treatment of NLRP3-associated diseases, including IL-1β/IL-18-driven inflammatory/autoinflammatory conditions [10,13] and other diseases that have an inflammatory component such as atherosclerosis [7,14], type 2 diabetes, Alzheimer's and Parkinson's diseases [8,12], cancer and pathologic inflammation that is a result of viral infection [1,11].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 117.02
Molecular weight 404.14
XLogP 2.66
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES O=C(NS(=O)(=O)c1occ(c1)C(O)(C)C)Nc1c2CCCc2cc2c1CCC2
Isomeric SMILES O=C(NS(=O)(=O)c1occ(c1)C(O)(C)C)Nc1c2CCCc2cc2c1CCC2
InChI InChI=1S/C20H24N2O5S/c1-20(2,24)14-10-17(27-11-14)28(25,26)22-19(23)21-18-15-7-3-5-12(15)9-13-6-4-8-16(13)18/h9-11,24H,3-8H2,1-2H3,(H2,21,22,23)
InChI Key HUUSXLKCTQDPGL-UHFFFAOYSA-N
References
1. Coates BM, Staricha KL, Ravindran N, Koch CM, Cheng Y, Davis JM, Shumaker DK, Ridge KM. (2017)
Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in Juvenile Influenza A Virus Infection.
Front Immunol, 8: 782. [PMID:28740490]
2. Coll RC, Hill JR, Day CJ, Zamoshnikova A, Boucher D, Massey NL, Chitty JL, Fraser JA, Jennings MP, Robertson AAB et al.. (2019)
MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.
Nat Chem Biol, 15 (6): 556-559. [PMID:31086327]
3. Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A et al.. (2015)
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.
Nat Med, 21 (3): 248-55. [PMID:25686105]
4. Corcoran SE, Halai R, Cooper MA. (2021)
Pharmacological Inhibition of the Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome with MCC950.
Pharmacol Rev, 73 (3): 968-1000. [PMID:34117094]
5. Dekker C, Mattes H, Wright M, Boettcher A, Hinniger A, Hughes N, Kapps-Fouthier S, Eder J, Erbel P, Stiefl N et al.. (2021)
Crystal Structure of NLRP3 NACHT Domain With an Inhibitor Defines Mechanism of Inflammasome Inhibition.
J Mol Biol, 433 (24): 167309. [PMID:34687713]
6. Fenini G, Contassot E, French LE. (2017)
Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases.
Front Pharmacol, 8: 278. [PMID:28588486]
7. Hettwer J, Hinterdobler J, Miritsch B, Deutsch MA, Li X, Mauersberger C, Moggio A, Braster Q, Gram H, Robertson AAB et al.. (2022)
Interleukin-1β suppression dampens inflammatory leucocyte production and uptake in atherosclerosis.
Cardiovasc Res, 118 (13): 2778-2791. [PMID:34718444]
8. Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, Schwartz S, Albasset S, McManus RM, Tejera D et al.. (2019)
NLRP3 inflammasome activation drives tau pathology.
Nature, 575 (7784): 669-673. [PMID:31748742]
9. Kennedy CR, Goya Grocin A, Kovačič T, Singh R, Ward JA, Shenoy AR, Tate EW. (2021)
A Probe for NLRP3 Inflammasome Inhibitor MCC950 Identifies Carbonic Anhydrase 2 as a Novel Target.
ACS Chem Biol, 16 (6): 982-990. [PMID:34003636]
10. Ni B, Pei W, Qu Y, Zhang R, Chu X, Wang Y, Huang X, You H. (2021)
MCC950, the NLRP3 Inhibitor, Protects against Cartilage Degradation in a Mouse Model of Osteoarthritis.
Oxid Med Cell Longev, 2021: 4139048. [PMID:34777685]
11. Tate MD, Ong JDH, Dowling JK, McAuley JL, Robertson AB, Latz E, Drummond GR, Cooper MA, Hertzog PJ, Mansell A. (2016)
Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition.
Sci Rep, 6: 27912. [PMID:27283237]
12. Wang S, Yuan YH, Chen NH, Wang HB. (2019)
The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson's disease.
Int Immunopharmacol, 67: 458-464. [PMID:30594776]
13. Wang Z, Zhang S, Xiao Y, Zhang W, Wu S, Qin T, Yue Y, Qian W, Li L. (2020)
NLRP3 Inflammasome and Inflammatory Diseases.
Oxid Med Cell Longev, 2020: 4063562. [PMID:32148650]
14. Zeng W, Wu D, Sun Y, Suo Y, Yu Q, Zeng M, Gao Q, Yu B, Jiang X, Wang Y. (2021)
The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages.
Sci Rep, 11 (1): 19305. [PMID:34588488]