BAY-707

Protein target name:

NUDT1

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

1 nM to 1 µM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Nudix Hydrolase

HUGO ID:

HGNC:8048

Entrez gene ID:

4521

UNIPROT ID:

P36639

Probe Details

Chemical Probes Portal ID:

CPP1858

Probe alias:

BAY707

PubChem CID:

129012086

ChEMBL ID:

CHEMBL4096813

SMILES string:

CCNC(=O)c1cc2c(N3CCOC[C@@H]3C)ccnc2[nH]1

InChi Key:

RPMGXDCRCWWCRY-JTQLQIEISA-N

Control compound:

BAY-604

Orthogonal probe:

TH588

Physico-chemical properties

NMR:

¹H NMR (400 MHz, DMSO-d6) δ ppm 1.11 (d, J=6.59 Hz, 3 H) 1.14 (t, J=7.22 Hz, 3 H) 3.30 (m, 2 H) 3.40 (m, 2 H) 3.57 - 3.68 (m, 1 H) 3.70 - 3.78 (m, 1 H) 3.80 - 3.87 (m, 1 H) 3.92 - 4.01 (m, 1 H) 4.23 - 4.32 (m, 1 H) 6.41 (d, J=5.58 Hz, 1 H) 7.24 (s, 1 H) 8.01 (d, J=5.58 Hz, 1 H) 8.33 (t, J=5.58 Hz, 1 H) 11.82 (br s, 1 H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

2.3 nM

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

5NHY

Structure-activity relationship:

Yes

Off target activity

Potency assay (off target):

Tm shift assay

Probe Selectivity in Vitro:

BAY-707 is a selective NUDT1 (MTH1) inhibitor across the Nudix family

In cell validation

On target activity in cells

Potency in cells:

EC50

7.6 nM

Potency assay (cells):

Isothermal concentration response curves were used to determine cellular target engagement potency

Off target activity in cells

Probe Selectivity in Cell:

high selectivity in an in-house kinase panel comprised of 30 kinases

In vivo validation

Organism:

Mouse MicrosomesHuman Microsomes

Dose:

25 mg/Kg250 mg/Kg

Systemic clearance:

0.3 L/h/kg

Fraction of probe bound to plasma protein:

78.4 %

Primary Reference

Reference (doi):

10.1021/acschembio.7b00370 10.1021/acs.jmedchem.7b01884

Reference (PMID):

28679043 29485874

External Resources

Available data:

SGC additional analysis

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

Part of the Donated Chemical Probes initiative from SGC.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

2 review(s)

SAB Members

SAB Comments

BAY-707 is a potent inhibitor of the NUTD1 (MHT1) hydrolase. It was selective across the Nudix family. However, additional selectivity data outside the Nudix family has not been published. Therefore, some caution should be used in interpreting phenotypic data. BAY-707 has been used in vivo, although only very limited dosing and pharmacokinetic data have been published.

Jun 28 2020 - 8:52am

BAY-707 is a potent, selective NUDT1 inhibitor that demonstrates enzymatic inhibition in vitro, and cellular target engagement in cells using CETSA. It does not demonstrate broad anti-cancer activity in cells nor activity in 2 in vivo mouse xenograft models (100 mg/kg oral dose). Double-stranded DNA breaks with compounds from this series are unlikely to result from direct target engagement. BAY-707 shows no effect on nuclear 8-oxo-dG levels.

Jul 26 2020 - 10:11am

BAY-707

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

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BAY-707

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?