IMP-1088

Protein target name:

NMT1, NMT2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

100 nM -1000 nM

Probe Availability

MedChemExpress

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:

CPP2351

Probe alias:

KFK

PubChem CID:

132274735

ChEMBL ID:

CHEMBL4445137

SMILES string:

CN1N=C(CN(C)C)C2=C1C=CC(C3=CC=C(F)C(F)=C3OCCC4=C(C)N(C)N=C4C)=C2

InChi Key:

SOXNKJCQBRQUMS-UHFFFAOYSA-N

Control compound:

IMP-994

Orthogonal probe:

IMP-366

Physico-chemical properties

NMR:

1H-NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 10.16 (s, 1H), 8.25 (d, J = 1.5 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.69 (dd, J = 8.8, 1.6 Hz, 1H), 7.18 (ddd, J = 8.6, 6.1, 2.1 Hz, 1H), 7.05 – 6.91 (m, 1H), 4.25 (s, 3H);

13C-NMR (101 MHz, Chloroform-d) δ 187.15, 150.29 (dd, J = 245.0, 10.8 Hz), 142.79 (dd, J = 248.3, 11.3 Hz), 142.47 , 140.75 , 139.76 (d, J = 14.4 Hz), 133.44 , 129.52 , 127.17, 125.88 – 124.97 (m), 121.70 , 121.40 , 111.08 , 107.71 (d, J = 16.7 Hz), 37.18.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50, KD

< 1 nM (F), < 0.210 nM (S)

Potency assay:

Fluorogenic detection of the CoASH (F)(NMT inhibition assay), SPR (S)

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

5MU6

Structure-activity relationship:

yes

In cell validation

On target activity in cells

Potency in cells:

IC50

17 nM (C), 5.8 nM (R)

Potency assay (cells):

Inhibition of virus-induced CPE (C), Inhibition of single-cycle replication in HeLa cells infected with RV-A16 (R)

Target engagement assay (cells):

Quantitative proteomic analysis of inhibition of protein myristoylation

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

No evidence of cytotoxicity

Primary Reference

Reference (doi):

10.1016/j.chembiol.2019.03.006 10.1038/s41557-018-0039-2

Reference (PMID):

31006618 29760414

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

The cited reference (10.1016/j.chembiol.2019.03.006) is an excellent comparative study of the 5 cmpds that have been used as NMT probes and shows clearly and conclusively that only IMP-1088 and IMP-366 ( DDD85646 ) are suitable to use as orthogonal probes in vitro and in cells for the human NMT1 and NMT2 targets. Of these two, IMP-1088 is clearly the more potent probe cmpd.

Jun 18 2021 - 9:55am

Proteomic data suggest that this compound has high specificity for NMT1 and NMT2, but genetic evidence for target specificity is still awaited. There is no information on its usefulness in animal models.

Jun 30 2021 - 9:13am

There is no selectivity data indicating that this compound inhibits the intended target(s) without inhibiting other acyltransferases. Looking at the chemical structure, I would anticipate activity on other target classes outside of the acyltransferases. In addition, there is no negative control compound that would raise the comfort level of using this compound as a chemical probe.

Jul 7 2021 - 12:42pm

IMP-1088

Probe Availability

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

Toxicity

Primary Reference

Supporting Organizations

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IMP-1088

Probe Availability

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

Toxicity

Primary Reference

Supporting Organizations

Interested in supporting the portal?