BAY-598

BAY-598 : protein-substrate competitive, SAM uncompetitive inhibitor of SMYD2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

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Information

SMYD2

protein-substrate competitive inhibitor, SAM uncompetitive inhibitor

50 nM - 2 uM

DOI - 10.1021/acs.jmedchem.5b01890

Probe Availability:

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

Off-Target Selectivity Assesments

Potency in cells, off target : IC50 SMYD3 3 uM

Potency assay, off target (cells): BAY-598 showed 100-fold selectivity for SMYD2 over 30 protein methyltranferases including SMYD3, SUV420H1, and SUV420H2.

Probe Selectivity in Cell:

No significant activity was detected in KINOMEscan (DiscoveRx) or LeadProfilingScreen (Eurofin Panlabs) assays.

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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

SERP 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

SERP 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 )