PF-9363

PF-9363 : Inhibitor of KAT6A, KAT6B

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 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.

Information

KAT6A
KAT6B

Inhibitor

up to 1 uM
Reviewer recommended concentration: 100 - 300 nM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q92794

Target Class: Epigenetic

Target SubClass: MYST family

Potency: Ki

Potency Value: 0.27 nM

Potency Assay: SPR

PDB ID for probe-target interaction (3D structure): 8DD5

Target aliases:

Histone acetyltransferase KAT6A, ZNF220, RUNXBP2, ...

DOI Reference: 10.1016/j.chembiol.2023.07.005

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): CTx-648 growth inhibitory activity was tested in a panel of 60 breast cancer cell lines

Potency assay (off target): Selective within target family: KAT7 (Ki 70 nM), KAT5 (Ki 420 nM) and KAT8 (Ki 670 nM)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is a good probe for this family of proteins.

(last updated: 12 Oct 2023 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

PF-9363 is a quality chemical probe for KAT6A/6B with exquisite potency and mouse PK. The overall selectivity is difficult to judge; KAT6B/KAT7 appears to be 29x based on binding and cellular selectivity is not straightforward to interpret with overlapping acetylation marks, based on literature data. Without clear in-cell TE selectivity remains a question and data points at higher concentration could become difficult to interpret. There is no broad off-target profiling data available for this compound; limited cell panel data has been published but all data taken together, there is no strong concern that data could be confounded by compound promiscuity. Surprisingly good mouse PK and a robust published biology package make this compound an interesting in vivo tool. Overall, this compound is the best available KAT6A/6B inhibitor and should be used without hesitation.

(last updated: 17 Oct 2023 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 27 Oct 2023 )