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

Under Review

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

Interested in supporting the portal?

Search form

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?