A-196

Substrate-competitive inhibitor, SAM non-competitive inhibitor of KMT5B, KMT5C

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 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

Protein target names: KMT5B, KMT5C

Mechanism of action: Substrate-competitive inhibitor, SAM non-competitive inhibitor

Primary References:

Probe Availability:

MedChem Express (A-196)

In Vitro Validations

Uniprot ID: Q4FZB7

Target Class: Epigenetic

Target SubClass: Protein methyltransferase

Potency: IC 50

Potency Value: 25 nM

Potency Assay: Scintillation proximity assay - Methyltransferase activity assays for SUV420H1 and SUV420H2 were performed by monitoring the incorporation of tritium-labeled methyl group to monomethylated lysine 20 of peptide H4(1-24) (H4K20Me1). The experiments were performed in triplicate.

PDB ID for probe-target interaction (3D structure): 5CPR

Structure-activity relationship: Yes, to be published separately

Target aliases:

Histone-lysine N-methyltransferase KMT5B, SUV420H1 ...

DOI Reference: 10.1038/nchembio.2282

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 15 Mar 2017 )

SERP Ratings

In Cell Rating

(last updated: 21 Mar 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe represents the best in class for SUV420H1 and H2 - hitting the enzymes at 25 and 144 nM, respectively, with selectivity data against a wide panel of related epigenetic and other targets. The originating paper gives good confidence around this molecule and includes strong biochemical, biophysical, structural & cellular data, as well as structurally related negative controls. No data are presented for the wider pharmacokinetic, drug-like profiles, and so no conclusion can be drawn on its suitability as a probe for use in model organism studies. However, permeability from cellular studies and chemical structure would support its further investigation towards these studies.

(last updated: 30 Mar 2017 )