TH5427

Inhibitor of NUDT5

Structure

Information

Protein target names: NUDT5

Mechanism of action: Inhibitor

Recommended in-cell concentration:
up to 1.5 uM

In Vitro Validations

Uniprot ID: Q9UKK9
Target Class: Epigenetic
Target SubClass: Nudix Hydrolase
Potency: IC50
Potency Value: 29 nM
Potency Assay: MG assay
PDB ID for probe-target interaction (3D structure): 5NWH
Structure-activity relationship: yes
Target aliases:
ADP-sugar pyrophosphatase, NUDIX5, NUDT5, NUDT5_HU ...

DOI Reference: 10.1038/s41467-017-02293-7

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

TH5427 is potent and selective chemical probe for NUDT5, a NUDIX hydrolase enzyme that plays important roles in the metabolism of adenosine-5’-diphisphoribose (ADPR) metabolism and regulation of hormone signaling. NUDT5 has been implicated in breast cancer, and TH5427 should provide a valuable tool for the continued exploration of the role of this target in breast cancer and other diseases models. TH5427 is at least 690-fold selective for NUDT5 over other NUDIX hydrolases in vitro, with only limited demonstrated interactions outside of the NUDIX hydrolyase family. I recommend the use of this probe in cells at concentrations up to 1.5 µM, with demonstrated effectiveness in HL-60 and T47D cells. TH5427 does show a large cellular potency offset comparing potency in vitro (malachite green assay, 29 nm) vs in cellular target engagement assays (CETSA and DARTS, 0.75-2.1 µM), though this potency offset has not been specifically explained (i.e. cellular availability vs metabolite competition or other factors).

(last updated: 11 Jul 2020 )

SERP Ratings

In Cell Rating

SERP Comments:

TH5427 showed 690-fold selectivity for NUDT5 over MTH1 in direct assay of ADP-ribose hydrolysis in vitro.

(last updated: 26 Jul 2020 )