(R,R)-59

Inhibitor of SETDB1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 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

SETDB1

Inhibitor

5-10 uM
Reviewer recommended concentration: Care should be taken at the recommended concentation KD for Tudor domain of 53BP1 is in the recommended concentration range

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q15047

Target Class: Enzyme

Target SubClass: methyltransferase

Potency: Kd

Potency Value: 88 ± 45 nM

Potency Assay: ITC

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

Target aliases:

Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1002/anie.202017200

Uniprot ID: Q15047

Target Class: Enzyme

Target SubClass: methyltransferase

Potency: Kd

Potency Value: 106 ± 2 nM

Potency Assay: SPR

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

Target aliases:

Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

PMID Reference: 33511756

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): 16 other Tudor domain proteins

Probe Selectivity in Vitro:

ITC used to determine the selectivity of (R,R)-59 against other Tudor domaining containing proteins; did not show activity against 14 of the 16 tested Tudor domains (KD>100 μM). 53BP1 and JMJD2A were the only two Tudor domain proteins for which (R,R)-59 showed some activity; the KD values were 4.3 μM and 86 μM, respectively; no activity or very weak activity against 32 BRD proteins using the DSF assay

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 3 Jan 2022 )

SERP Ratings

In Cell Rating

SERP Comments:

Care should be taken at the recommended concentration as the KD for the Tudor domain of 53BP1 is in the recommended concentration range.

(last updated: 19 Jan 2022 )

SERP Ratings

In Cell Rating

SERP Comments:

To target the TTD domain of SETDB1, this compound is the best available. Meanwhile, the caution should be hold about the effective concentration for target engagement, which was studied with the TTD domain of SETDB1 rather than full-length SETDB1. Users should be aware about potential off-target effects beyond Tudor and BRD domains. The outcomes of this compound should be collectively evaluated in combination with other information.

(last updated: 31 Jan 2022 )