AS-99

Inhibitor, SET non-competitive of ASH1L

Structure

Information

Protein target names: ASH1L

Mechanism of action: Inhibitor, SET non-competitive

Recommended in-cell concentration:
up to 6 uM

In Vitro Validations

Uniprot ID: Q9NR48
Target Class: Epigenetic
Target SubClass: HMT
Potency: IC50, KD
Potency Value: 790 nM; 890 nM
Potency Assay: Histone methyltransferase radioactivity assay, ITC
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Histone-lysine N-methyltransferase ASH1L, KMT2H, K ...

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

Comments:

AS-99 is the first selective ASH1L inhibitor and an excellent chemical probe.

(last updated: 29 Jun 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

The active compound is a thioamide, metabolic to inactive amide may apply dependent on animal model but good PK was shown in this study.

(last updated: 5 Jul 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

ASH1 is an important epigenetic target. Before this report, there is no high-quality ASH1 inhibitor.  AS-99 is the first small-molecular inhibitor of ASH1 with a decent IC50 and promising cellular activity. This compound and its negative control have been well characterized in vitro and in cells regarding the potency, selectivity, and modes of interaction. While the EC50 of AS-99 is modest, this compound has its merit against ASH1 in a cellular context because of the lack of inhibitors against the target. Please note that only the GI50 of AS-99 was reported and its cellular EC50 needs to be evaluated case by case.

(last updated: 6 Jul 2021 )