BAY-6035

BAY-6035 : apeptide-competitive inhibitor of SMYD3

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe BAY-6035 is in the process of SERP review.

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Information

SMYD3

peptide-competitive

~~1 uM~~
Reviewer recommended concentration: 5-10µM could be used as no toxicity has been observed up to 20 µM

Additional Data

SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: Q9H7B4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: ΔTm

Potency Value: 8.34 K

Potency Assay: Thermal Shift Assay

PDB ID for probe-target interaction (3D structure): 7O2C

Target aliases:

Histone-lysine N-methyltransferase SMYD3, ZNFN3A1, ...

DOI Reference: 10.1177/24725552211019409

Uniprot ID: Q9H7B4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: IC50

Potency Value: 88 nM

Potency Assay: Scintillation Proximity Assay

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

Target aliases:

Histone-lysine N-methyltransferase SMYD3, ZNFN3A1, ...

DOI Reference: 10.1177/24725552211019409

Uniprot ID: Q9H7B4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: Kd

Potency Value: 133 nM

Potency Assay: ITC

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

Target aliases:

Histone-lysine N-methyltransferase SMYD3, ZNFN3A1, ...

DOI Reference: 10.1177/24725552211019409

Uniprot ID: Q9H7B4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: Kd

Potency Value: 97 nM

Potency Assay: SPR

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

Target aliases:

Histone-lysine N-methyltransferase SMYD3, ZNFN3A1, ...

DOI Reference: 10.1177/24725552211019409

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity was assessed against a set of 34 protein methyltransferases, including several that contained a SET domain and three DNA methyltransferases: BAY-6035 showed highly selective inhibition of SMYD3 with no activity on other methyltransferases. Outside target family: BAY-6035 was tested on a set of >30 different kinases and showed no significant inhibitory activity.

Potency assay, off target (cells): BAY-6035 was used to explore if inhibition of SMYD3 leads to inhibition of proliferation in 13 selected cell line models, including two non-cancer-derived models. In all tested cell lines, SMYD3 inhibition with BAY-6035 up to 20 µM did not impact cellular proliferation.

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 14 Feb 2023 )

SERP Ratings

In Cell Rating

SERP Comments:

This is a well validated probe molecule which surpasses many of the SGC set criteria for potency and selectivity, and a very weak binding control compound is included. It has been through several key off target profiling assays and has been shown to be selective in both in vitro and cellular contexts.

(last updated: 21 Feb 2023 )