WM-3835

WM-3835 : Inhibitor of KAT7

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe WM-3835 is in the process of SERP review.

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Information

KAT7

Inhibitor

3 uM
Reviewer recommended concentration: Concentration in cells may need to be higher than 3 uM in certain experiments, and users should confirm sufficient efficacy in their models.

Probe Availability:

In Vitro Validations

Uniprot ID: O95251

Target Class: Epigenetic

Target SubClass: Histone Acetyltransferase

Potency: IC50

Potency Value: 30 nM

Potency Assay: Biochemical (acetyltransferase) assay

PDB ID for probe-target interaction (3D structure): 6MAJ

Target aliases:

, Histone acetyltransferase KAT7, MYST2, HBOa, HBO ...

DOI Reference: 10.1038/s41586-019-1835-6

Uniprot ID: O95251

Target Class: Epigenetic

Target SubClass: Histone Acetyltransferase

Potency: Kd

Potency Value: 34 nM

Potency Assay: SPR

PDB ID for probe-target interaction (3D structure): --

Target aliases:

, Histone acetyltransferase KAT7, MYST2, HBOa, HBO ...

DOI Reference: 10.1038/s41586-019-1835-6

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Off Target: KAT6A

Potency end-point : IC50 17 nM

Probe Selectivity in Vitro:

biochemical assay and SPR (Kd = 7 nM)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 22 Feb 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

WM-3835 is an excellent chemical probe for HBO1. It should be used alongside its inactive control analog, WM-2474, whenever possible. Strengths of validation data include its robust SAR, nanomolar biochemical potency, strong evidence of target engagement (SPR, XR), and low micromolar cell activity. In terms of cellular activity, several readouts are consistent with engagement of its proposed target, including phenocopying the molecular and cellular effects of genetic depletion of HBO1 and reduction in the cellular H3K14ac biomarker. It has limitations in terms of efficacy in in vivo models due to its rapid metabolism, which the original report notes. While this represents the best quality HBO1 probe to-date (the results of excellent medicinal chemistry and cancer biology teamwork), additional validation data with respect to biochemical and cellular off-targets, as well as its effects on cellular health in additional models and cell lines, would add more confidence to its use.

(last updated: 26 Feb 2022 )