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].
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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.

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View interactive charts of activity data across species
2D Structure
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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.

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Physico-chemical Properties
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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.

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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
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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.

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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
Bioactivity Comments
MCC950 is active against canonical NLRP3 stimuli such as lipopolysaccharide (LPS), nigericin or monosodium urate crystals, causing inhibition of stimulus-induced IL-1β release (IC50 8.1nM for LPS-induced IL-1β release in human monocyte-derived macrophages) [3]. NLRP3-induced responses to noncanonical stimuli (eg the Toll-like receptor 2/1 ligand Pam3CSK4 and intracellular LPS) are also inhibited by MCC950 [3]. MCC950 inhibits IL-1β and caspase-1 processing in ex-vivo cells from patients with Muckle-Wells syndrome, a type of pyrin-associated periodic syndrome (CAPS).
Carbonic anhydrase 2 (CA2) appears to be an off-target [9].
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
NLRP3 Hs Inhibitor Inhibition >8.0 pIC50 - 3
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [3]