RTx-161

RTx-161 : Allosteric Inhibitor of POLQ

Structure

SERP Rating

In Cells

(2 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.

Probe RTx-161 is in the process of SERP review.

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Information

POLQ

Inhibitor

up to 10 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: O75417

Target Class: Enzyme

Target SubClass: DNA Polymerase

Potency: IC50

Potency Value: 4.1 nM

Potency Assay: Biochemical DNA synthesis assay

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

Target aliases:

DNA polymerase theta, POLH, POLQ, DPOLQ_HUMAN, DNA ...

DOI Reference: 10.1038/s41467-024-46593-1

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selective against other 6 Polymerases.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

RTx-161 is an inhibitor of Polθ polymerase activity that exhibits biochemical IC50 of ~4nM. Thus, this compound could be used in biochemical and biophysical studies. In terms of the data supporting its use in cell-based assays, the compound seem to be active at IC50 of ~ 1-5uM in BRCA2 -/- cell lines. In order to classify this compound as a chemical probe for Polθ polymerase activity in cell-based assays, the following would need to be provided: - Negative control compound(s), and direct comparison with the NC compound(s) - Additional selectivity data beyond the small panel of closely related DNA pols was included, and comparison with NC - Additional evidence for cellular target engagement, and comparison with NC. RTx-161 does not compare well with ART558/ART615 (probe/NC compound) pair, so ART558 remains the probe to recommend over this one.

(last updated: 12 Jun 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

The compound is potent and on-target activity is well demonstrated but selectivity profiling is quite limited and a negative control is missing.

(last updated: 14 Jun 2024 )