VVD-214

VVD-214 : Covalent allosteric inhibitor of WRN

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 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.

Probe VVD-214 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

Allosteric

up to 1 uM

In Vitro Validations

Uniprot ID: Q14191

Target Class: Enzyme

Target SubClass: Helicase

Potency: IC50

Potency Value: 142 nM

Potency Assay: Helicase DNA unwinding assay using full length WRN in presence of ATP; Kinact >15 s-1; Ki > 15 µM

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

Target aliases:

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

DOI Reference: 10.1038/s41586-024-07318-y

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): No activity on related BLM helicase in helicase DNA unwinding assay

Potency assay (off target): Targeted mass spectrometry-based chemoproteomics method

Probe Selectivity in Vitro:

Selectively engagement of C727 on WRN

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The compound contains a somewhat reactive electrophile and gives good target engagement at 1 uM so no need to go higher. It does hit a few cysteines on other proteins according to Extended Figure 1c, so higher concentrations may lead to off-target effects. Overall, this is a good covalent probe for WRN. A good non-covalent probe against the same target is HRO761.

(last updated: 31 Jul 2024 )