GSK-J4

GSK-J4 : pro-drug, competitive with Akg, noncompetitive with peptide substrate of KDM6A, KDM6B

Structure

Information

Protein target names: KDM6A, KDM6B

Mechanism of action: pro-drug, competitive with Akg, noncompetitive with peptide substrate

Primary References:

In Vitro Validations

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

I could not find a broad selectivity assessment of GSK-J4 or its active carboxylic acid form. A broader assessment of the ester prodrug and the carboxylate is necessary before using this compound as an in vivo tool; thus, this is not an ideal tool molecule. I recommend using it for cellular studies only.

(last updated: 14 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

GSK-J4 is the ester prodrug of the active (acid) component GSK-J1. The ester is designed to facilitate entry into cells where it is rapidly hydrolysed to the active acid and studies from the authors demonstrate rapid hydrolysis in macrophages, the systems studied. They also note that in other cell systems, the degree and rate of conversion to acid should be assessed to ensure data generated is not misleading. It is a cell active inhibitor of KDM6 although more recently it has been demonstrated to exhibit inhibition of KDM5, albeit weaker. It can be recommended as a cell target probe with the caveats around moderate KDM selectivity, dependence on ester cleavage for activity, and also a not ideal level of target potency even when hydrolysed in cells.

(last updated: 20 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Tested in mice at 5mg/kg delivery by i.p. injection (https://doi.org/10.1093/hmg/ddu376) as well as at 0.5mg/kg by i.p injection ( 10.1186/s13075-018-1560-9) therefore recommend 0.5-5 mg/kg i.p. in mice.

(last updated: 16 Nov 2020 )