HRO761

HRO761 : allosteric inhibitor of WRN

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe HRO761 is in the process of SERP review.

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Information

allosteric

up to 1 µM

In Vitro Validations

Uniprot ID: Q14191

Target Class: Enzyme

Target SubClass: Helicase

Potency: IC50

Potency Value: 100 nM

Potency Assay: ATPase assay at high ATP

PDB ID for probe-target interaction (3D structure): 8PFO

Target aliases:

Bifunctional 3'-5' exonuclease/ATP-dependent helic ...

DOI Reference: 10.1038/s41586-024-07350-y

Uniprot ID: Q14191

Target Class: Enzyme

Target SubClass: Helicase

Potency: IC50

Potency Value: 9 nM

Potency Assay: ATP binding

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

Target aliases:

Bifunctional 3'-5' exonuclease/ATP-dependent helic ...

DOI Reference: 10.1038/s41586-024-07350-y

Uniprot ID: Q14191

Target Class: Enzyme

Target SubClass: Helicase

Potency: IC50

Potency Value: Helicase activity

Potency Assay: 40 nM

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

Target aliases:

Bifunctional 3'-5' exonuclease/ATP-dependent helic ...

DOI Reference: 10.1038/s41586-024-07350-y

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): Proliferation inhibition of HRO761 for a panel of cell lines

Potency assay (off target): HRO-761 was tested in biochemical assays against other helicases (RecQ helicases BLM, RecQ1 and RecQ5) and proved itself to be inhactive (IC50s >100 uM).

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

HRO761 is a potent allosteric inhibitor of WRN helicase. Despite it's high molecular weight and expected limitations in aqueous solubility, HRO761 has a convincing overall profile. It's selective activity in MSI high vs. MSS conditions is supportive for the considered MoA. On an enzymatic level, the selectivity claim is supported by RecQ selectivity data against RecQ1, BLM and RecQ5. However, a broader off-target profiling is not available. Therefore, VVD-214, a covalent WRN helicase inhibitor, is recommended as an orthogonal probe for cellular and in vivo applications.

(last updated: 8 Aug 2024 )

SERP Ratings

In Cell Rating

(last updated: 11 Aug 2024 )