ATX968

ATX968 : Inhibitor of DHX9

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe ATX968 is in the process of SERP review.

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Information

DHX9

Inhibitor

up to 1 uM

In Vitro Validations

Uniprot ID: Q08211

Target Class: Enzyme

Target SubClass: Helicase

Potency: Kd

Potency Value: 1.3 ± 0.3 nM

Potency Assay: DHX9 SPR binding assay

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

Target aliases:

ATP-dependent RNA helicase A, NDH2, DDX9, DHX9, DH ...

DOI Reference: 10.1158/0008-5472.CAN-24-0397

Uniprot ID: Q08211

Target Class: Enzyme

Target SubClass: Helicase

Potency: IC50

Potency Value: 8 ± 3 nM

Potency Assay: Helicase unwinding assay

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

Target aliases:

ATP-dependent RNA helicase A, NDH2, DDX9, DHX9, DH ...

DOI Reference: 10.1158/0008-5472.CAN-24-0397

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): A screen of 97 kinases (KINOMEscanEDGE™) was performed by Eurofins DiscoverX Corporation. ATX968 was screened at a concentration of 10 µM. Only DYRK1B showed inhibition <35% (24%)

Potency assay, off target (cells): ATX968 was profiled in a large panel of cancer cell lines from multiple lineages in a 10-day proliferation assay. Within this cell panel screen, MSI-H/dMMR CRC cell lines were more sensitive to ATX968 antiproliferative activity than MSS/pMMR CRC cell lines, confirming DHX9 dependency by compound inhibition across many different CRC cell models.

Potency assay (off target): ATX968 does not significantly inhibit DHX36, SMARCA2 or WRN helicase activity (measured by ADP-Glo™ assay) up to concentrations of 10 or 100 µM (inhibition <50% at top concentration tested)

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

ATX968 is a potent inhibitor of DHX9 with expected downstream pharmacology and confirmed on-target binding by SPR. In the absence of selectivity data against other helicases or ATPases, the differentiated cellular activity in MSI and MSS cell lines is supporting the selectivity of ATX968 as a suitable DHX9 probe. The paper is focusing on ATX968. Additional information on inactive analogs, alternative DHX9 inhibitors from different structural classes or a co-crystal structure would have further increased the confidence. Accent Therapeutics entered clinical phase 1 with a different (and as of today structurally undisclosed) molecule (ATX559) in Dec. 2024.

(last updated: 15 Jan 2025 )