BAY-598

protein-substrate competitive inhibitor, SAM uncompetitive inhibitor of SMYD2

Structure

Information

Protein target names: SMYD2

Mechanism of action: protein-substrate competitive inhibitor, SAM uncompetitive inhibitor

Recommended in-cell concentration:
50 nM - 2 uM

In Vitro Validations

Uniprot ID: Q9NRG4
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: IC50
Potency Value: 27 nM
Potency Assay: Scintillation proximity assay
PDB ID for probe-target interaction (3D structure): 5ARG
Structure-activity relationship: Yes, at least 15 compounds with in vitro IC50 data.
Target aliases:
N-lysine methyltransferase SMYD2, KMT3C, SMYD2, SM ...

DOI Reference: 10.1021/acs.jmedchem.5b01890

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 17 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

In KYSE-150 cells, BAY-598 reduces p53K370me (relative to p53K370) with IC50 = 50 nM. Use BAY-598 in parallel with its control compound BAY-369 in cell assays.

(last updated: 18 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

This is a potent, selective probe suitable for cellular studies with on-target activity expected between 50-1000 nM. If used above 5000 nM, there is a potential for SMYD3 inhibition (unconfirmed). The probe is also suitable for use in vivo in human tumour xenografts in mice with on-target activity expected between 30-100 mg/kg (oral dosing). Full mouse PK, plasma protein binding, and free drug PK-PD relationships in mouse models have not yet been reported.  I recommend that the user determine free-drug exposure if dosing above 100 mg/kg (orally) to relate to pharmacology profile. Over the short term (48 h), the compound is chemically stable in standard conditions; racemisation has been observed in basic forcing conditions.

(last updated: 4 Jun 2016 )