TAK-981

Protein target name:

SAE1, UBA2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

Up to 1 uM, followed by washout

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

AOS1, HSPC140, SUA1, UBLE1A, ARX, SAE2, HRIHFB2115

Probe Details

Chemical Probes Portal ID:

CPP2276

Probe alias:

Subasumstat, cpd 49

PubChem CID:

118628567

SMILES string:

O=S(OC[C@@H]1[C@@H](O)C[C@H](NC2=NC=NC=C2C(C3=CC([C@@H]4NCCC5=C4C=C(Cl)C=C5)=C(C)S3)=O)C1)(N)=O

InChi Key:

LXRZVMYMQHNYJB-UNXOBOICSA-N

Physico-chemical properties

Solubility - concentration:

20 000 ug/ml

NMR:

1H NMR (MeOD) δ 8.63 (s, 1H), 8.53 (s, 1H), 7.29 (s, 1H), 7.17 (s, 2H), 6.71 (s, 1H), 5.23 (s, 1H), 4.83–4.69 (m, 1H), 4.32–4.07 (m, 3H), 3.40–3.23 (m, 1H), 3.12–2.94 (m, 2H), 2.90–2.75 (m, 1H), 2.61 (s, 3H), 2.55–2.39 (m, 1H), 2.33–2.19 (m, 1H), 2.18–2.09 (m, 1H), 1.96–1.78 (m, 1H), 1.50–1.34 (m, 1H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

1 nM

Potency assay:

The E1-E2 HTRF transthiolation (HTRF)

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

6XOH

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

IC50s of NAE and UAE are 960 and > 1000 nM, respectively.

In cell validation

On target activity in cells

Potency in cells:

IC50

15 nM, (32 - 46 nM, 0 - 8 h)

Potency assay (cells):

SUMO2/3 immunofluorescent Assay assessing the ration of SUMO2/3 in the nuclear versus cytoplasm (treatment is followed by immediate washout and readings at 0 and 8 h)

In vivo validation

Organism:

Rat

Dose:

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

Route of delivery:

IntravenousSubcutaneous

Plasma half life:

2.6 (B), 2.1 (P) h

Systemic clearance:

0.1 (B), 3.7 (P) L/h/Kg

Vss:

0.2 (B), 8.5 (P) L/Kg

AUC:

32.0 (B), 0.3 (P) uM*h PO, 31.2 (B), 0.5 (P) uM*h IV

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.0c01491

Reference (PMID):

33631934

TAK-981

Probe Availability

Probe Information

Target Details

AOS1, HSPC140, SUA1, UBLE1A, ARX, SAE2, HRIHFB2115

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?

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TAK-981

Probe Availability

Probe Information

Target Details

AOS1, HSPC140, SUA1, UBLE1A, ARX, SAE2, HRIHFB2115

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?