GSK2973980A

Inhibitor of DGAT1

Structure

Information

Protein target names: DGAT1

Mechanism of action: Inhibitor

In Vitro Validations

Uniprot ID: O75907
Target Class: Other
Target SubClass: Diacylglycerol O-acyltransferase
Potency: IC50
Potency Value: 3.3 (human), 13 (rat) nM
Potency Assay: Radiometric lipid extraction assay (enzymatic assay)
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Diacylglycerol O-acyltransferase 1, DGAT, AGRP1, D ...

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

Comments:

Regarding the doses used in vivo and mode of delivery, one needs to think about the goal of the experiment. The authors observed high inhibition of triglyceride synthesis in mice at a low dose of 0.088 mg/kg mostly due to DGAT1 inhibition in the GI tract where the compound’s concentration is likely to be significantly higher during drug absorption following oral dosing. Studying compound effect a few hours (4 and 15 selected by the authors) after dosing or using a parenteral route of administration are ways to evaluate systemic DGAT1 inhibition without the effect on enterocytes during compound absorption.

(last updated: 20 May 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

GSK2973980A has an acceptable in-vitro profile against its primary target and the off-targets that have been explored. There remains the possibility of in-vivo effects (desired efficacy and safety/toxicity) are due to poly-pharmacology, therefore it is suggested that additional data is generated. This could include profiling of GSK2973980A against a panel of protein targets from a variety of classes.

(last updated: 5 Aug 2021 )