DDD85646

Protein target name:

NMT1, NMT2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 100 nM

Probe Information

Target and Probe Information

Target Details

Target class:

alternative, short form NMT-S, long form, NMT-L, myristoyl-CoA:protein N-myristoyltransferase, NMT,

Probe Details

Chemical Probes Portal ID:

CPP739

Probe alias:

IMP-366

PubChem CID:

44199337

ChEMBL ID:

CHEMBL1230468

SMILES string:

CC1=C(C(=NN1C)C)NS(=O)(=O)C2=C(C=C(C=C2Cl)C3=CC(=NC=C3)N4CCNCC4)Cl

InChi Key:

XMBSZPZJLPTFMV-UHFFFAOYSA-N

Orthogonal probe:

IMP-1088

Physico-chemical properties

NMR:

1H NMR (500 MHz, DMSO-d6): δ 9.79 (s, 1H), 8.25 (d, J = 5.9 Hz, 1H), 8.20 (s, 2H), 7.61 (s, 1H), 7.40 (d, J = 5.9 Hz, 1H), 4.08 (s br, 4H), 3.63 (s, 3H), 3.28 (s br, 4H), 2.00 (s, 3H), 1.77 (s, 3H).

13C NMR (125 MHz, DMSO-d6): 147.5, 147.3, 143.8, 137.4, 136.3, 135.2, 129.8, 111.8, 111.7, 109.1, 108.9, 42.7, 42.0, 36.2, 10.4.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50KD

2 nM TbNMT, 3 nM HsNMT-1, 2 nM LmNMT, 3 nM TcNMT; 1 nM TbNMT, 14 nM HsNMT-1 KD

Potency assay:

NMT enzyme assay, SPR (KD)

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

2WSA

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

Not selective across species in vitro (biochemical assay).

In cell validation

On target activity in cells

Potency in cells:

EC50

2 nM Tb

Potency assay (cells):

trypanocidal activity in cultured T. brucei

Off target activity in cells

Probe Selectivity in Cell:

DDD85646 shows promising selectivity at the cellular level

In vivo validation

Organism:

Mouse

Dose:

3 mg/Kg IV10 mg/Kg POup to 50 mg/Kg

Route of delivery:

OralIntravenous

Plasma half life:

1.2 h

Systemic clearance:

6 mL/min/Kg

Primary Reference

Reference (doi):

10.1038/nature08893 10.1021/jm201091t

Reference (PMID):

20360736 22148754

DDD85646

Probe Information

Target Details

alternative, short form NMT-S, long form, NMT-L, myristoyl-CoA:protein N-myristoyltransferase, NMT,

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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DDD85646

Probe Information

Target Details

alternative, short form NMT-S, long form, NMT-L, myristoyl-CoA:protein N-myristoyltransferase, NMT,

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?