GSK2194069

Inhibitor of FASN

Structure

Information

Protein target names: FASN

Mechanism of action: Inhibitor

Recommended in-cell concentration:
100 nM

In Vitro Validations

Uniprot ID: P49327
Target Class: Lipid metabolism
Target SubClass: Synthase
Potency: IC50
Potency Value: 7.7 ± 4.1 nM
Potency Assay: Endpoint assay for thiols using a fluorescent maleimide
PDB ID for probe-target interaction (3D structure): 4PIV
Structure-activity relationship: yes
Target aliases:
Fatty acid synthase, FAS, FASN, FAS_HUMAN, Type I ...

DOI Reference: 10.1038/nchembio.1603

Uniprot ID: P49327
Target Class: Lipid metabolism
Target SubClass: Synthase
Potency: Ki
Potency Value: 5 nM
Potency Assay: Stopped-flow experiments
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Fatty acid synthase, FAS, FASN, FAS_HUMAN, Type I ...

DOI Reference: 10.1038/nchembio.1603

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

Comments:

An excellent probe for FASN but, as PK data is missing, it is hard to judge the in vivo dosing. 

(last updated: 7 Sept 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

GSK2194069 is a potent probe for the beta-ketoacyl reductase domain of hFAS, and has the potential to be useful in exploring the role of fatty acid synthesis in tumour proliferation. Its inhibition of the KS domain is well characterized kinetically and is competitive with the substrate, but not NADPH co-factor. This is verified structurally. In vitro activity is well explored across several cancer cell lines, and is shown to inhibit lipid synthesis at low doses. There is a limited investigation of the selectivity, therefore this compound is more useful as an orthogonal probe as opposed to a high-quality probe in its own right. In vivo investigations were limited to investigation in one organism with one dosing protocol, although tumour volume was shown to decrease more in vivo data such as full PK profile are needed before recommending for in vivo use.

(last updated: 13 Sept 2021 )