LSN 3213128

Protein target name:

ATIC

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 200 nM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Metabolic Enzyme

Subclass:

formyltransferase and cyclohydrolase

HUGO ID:

HGNC:794

Entrez gene ID:

471

UNIPROT ID:

P31939

Target alias:

PURH; AICAR; AICARFT; IMPCHASE; HEL-S-70p

Probe Details

Chemical Probes Portal ID:

CPP2059

Probe alias:

8US, 28a

PubChem CID:

121378588

ChEMBL ID:

CHEMBL4063104

SMILES string:

O=C1NC=CC2=C1C=C(NS(=O)(C3=CC=C(N4CC[C@@H](O)C4)S3)=O)C(F)=C2

InChi Key:

DSUZLJDXUJUTGI-LLVKDONJSA-N

PAINs evaluation:

PAINS-Free

Physico-chemical properties

NMR:

1H NMR (400 MHz, DMSO-d6): δ 11.27−11.26 (m, 1H), 10.06 (s, 1H), 8.10 (m, 1H), 7.45 (m, 1H), 7.14−7.11 (m, 2H), 6.44−6.42 (m, 1H), 5.66 (m, 1H), 5.05 (m, 1H), 4.40−4.30 (m, 1H), 3.40−2.90 (m, 4H), 2.10−1.80 (m, 2H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

16 ± 11 nM

Potency assay:

Enzymatic Assay

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

5UZ0

Structure-activity relationship:

yes

Off target activity

Potency assay (off target):

Enzymatic Assay, Eurofins

Probe Selectivity in Vitro:

Selective for AICARFT with IC50s >100 μM against TS, SHMT1, MTHFD1, MTHFD2 and MTHFD2L. The compound has been profiled in a panel of protein kinase assays at CEREP Panlabs (Eurofins) and has no significant protein kinase activity.

In cell validation

On target activity in cells

Potency in cells:

IC50

19 ± 8 nM

Potency assay (cells):

ZMP accumulation in Vitro Assay

In vivo validation

Organism:

Male CD-1 mice

Dose:

1 mg/Kg (IV)10 mg/Kg (PO)

Route of delivery:

OralIntravenous

Plasma half life:

1.4 h (PO)

Systemic clearance:

78 ML/min/Kg (IV)

Fraction of probe bound to plasma protein:

25 %

Cmax:

289 nM

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.7b01046 10.1038/s41598-018-33453-4

Reference (PMID):

29072452 30337562

LSN 3213128

Probe Availability

Probe Information

Target Details

PURH; AICAR; AICARFT; IMPCHASE; HEL-S-70p

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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LSN 3213128

Probe Availability

Probe Information

Target Details

PURH; AICAR; AICARFT; IMPCHASE; HEL-S-70p

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?