MCC950

Protein target name:

NLRP3

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

50 nM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

NACHT, LRR and PYD domains-containing Protein

Subclass:

NACHT, LRR and PYD domains-containing Protein

HUGO ID:

HGNC:16400

Entrez gene ID:

114548

UNIPROT ID:

Q96P20

Target alias:

AII; AVP; FCU; MWS; FCAS; KEFH; CIAS1; FCAS1; NALP3; C1orf7; CLR1.1; DFNA34; PYPAF1; AGTAVPRL

Probe Details

Chemical Probes Portal ID:

CPP1862

Probe alias:

MCC-950, CP-456773, CRID3

PubChem CID:

9910393

ChEMBL ID:

CHEMBL3183703

SMILES string:

O=S(C1=CC(C(C)(O)C)=CO1)(NC(NC2=C3CCCC3=CC4=C2CCC4)=O)=O

InChi Key:

HUUSXLKCTQDPGL-UHFFFAOYSA-N

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

224 nM

Potency assay:

SPR

Off target activity

Probe Selectivity in Vitro:

MCC950 does not inhibit NLRC4, AIM2, NLRP3 priming or Toll-like receptor signaling

In cell validation

On target activity in cells

Potency in cells:

IC50

7.5 nM BMDM8.1 nM HMDM

Potency assay (cells):

Inhibition of IL-1β secretion followed by Western Blot, ELISA and LDH assay

Off target activity in cells

Probe Selectivity in Cell:

MCC950 does not inhibit NLRC4, AIM2, NLRP3 priming or Toll-like receptor signaling

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

Cytotoxicity assessed for HEK293 CC50 >62.5 μM, HepG2 CC50 >62.5 μM

In vivo validation

Organism:

Mouse

Dose:

3 mg/Kg (IV)20 mg/Kg (PO)

Route of delivery:

OralIntravenous

Plasma half life:

3.27 h

Fraction of probe bound to plasma protein:

68%

Cmax:

25.3 ng/ml

Primary Reference

Reference (doi):

10.1021/acsmedchemlett.6b00198 10.1038/nm.3806 10.1038/s41589-019-0278-6 10.1038/s41589-019-0277-7

Reference (PMID):

27994733 25686105 31086329 31086327

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

1 review(s)

Rating for use in Model Organisms

1 review(s)

SAB Members

SAB Comments

This probe has been tested in human primary cell-based assays (BioMAP Diversity PLUS panel from Eurofins Discovery) at 370 – 10 uM. Selectively active in only one of the 12 assay systems at 370 nM, 1.1 uM and 3.3 uM. Activity is restricted to the BioMAP LPS system, a co-culture stimulated with LPS, so consistent with the target. It was not active in a system containing differentiated macrophages stimulated through TLR2.

Sep 15 2020 - 8:32am

MCC950

Probe Availability

Probe Information

Target Details

AII; AVP; FCU; MWS; FCAS; KEFH; CIAS1; FCAS1; NALP3; C1orf7; CLR1.1; DFNA34; PYPAF1; AGTAVPRL

Probe Details

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

Supporting Organizations

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MCC950

Probe Availability

Probe Information

Target Details

AII; AVP; FCU; MWS; FCAS; KEFH; CIAS1; FCAS1; NALP3; C1orf7; CLR1.1; DFNA34; PYPAF1; AGTAVPRL

Probe Details

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?