SGX-523

ATP-competitive inhibitor of MET

Structure

Information

Protein target names: MET

Mechanism of action: ATP-competitive inhibitor

Recommended in-cell concentration:
1 nM - 1 uM

In Vitro Validations

Uniprot ID: P08581
Target Class: Kinase
Target SubClass: TK
Potency: Ki
Potency Value: 2.7 nM
Potency Assay: In vitro kinase assay IC50 = 4 nM
PDB ID for probe-target interaction (3D structure): 3DKF
Target aliases:
Hepatocyte growth factor receptor, MET, MET_HUMAN, ...

DOI Reference: 158/1535-7163.MCT-09-0477

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

In vitro potency data against MET are for the kinase domain only and not the full-length enzyme.

(last updated: 2 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

SGX523 potently inhibited MET with an IC50 of 4 nM and is >250-fold selective versus 213 other protein kinases, representing approximately half of all catalytically competent human protein kinases and three quarters of all human protein tyrosine kinases. Cellular activity against MET-dependent cell lines was reported as EC50 = 5-113 nM. In vivo target engagement and tumor-growth inhibition were reported following oral administration to mice (10-100 mg/kg dosed twice daily).

(last updated: 20 Jun 2016 )

SERP Comments:

From a chemists point of view, this compound is a good probe.

(last updated: 13 Oct 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Selectivity and cellular activity are appropriate for use of this compound as a probe.

(last updated: 21 Dec 2016 )

SERP Comments:

This is an excellent probe molecule. It was highlighted in the famous Nature Biotechnology kinase inhibitor article (Nature Biotechnology 2011, 29, 1046–1051) as one of the most selective kinase inhibitors known. It shows both pharmacodynamic and functional cellular potency in line with its biochemical data as well as robust dose-responsive tumor-growth inhibitory effects in relevant xenograft mouse models. In terms of pre-clinical species, there are no limitations using this compounds in rodents and dog.

(last updated: 26 Dec 2016 )