AGI-6780

Allosteric inhibitor, uncompetitive with NADPH, noncompetitive with alphaKG substrate of IDH2 (R140Q)

Structure

Information

Protein target names: IDH2 (R140Q)

Mechanism of action: Allosteric inhibitor, uncompetitive with NADPH, noncompetitive with alphaKG substrate

In Vitro Validations

Uniprot ID: P48735
Target Class: Other
Target SubClass: Dehydrogenase
Potency: IC 50
Potency Value: 23 nM R140Q
Potency Assay: Enzymatic assay
PDB ID for probe-target interaction (3D structure): 4JA8
Target aliases:
Isocitrate dehydrogenase [NADP], mitochondrial, ID ...

DOI Reference: 10.1126/science.1234769

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

AGI-6780 currently represents the most appropriate probe molecule for the target; at the present time, the only literature (aside from the quoted 2013 Science paper) disclosing small-molecule inhibitors of the target are patents. The probe molecule should be used in the context of a relatively narrow published dataset, a specific caveat is that selectivity screening outside of a narrow range of closely related targets has not yet been reported.

(last updated: 28 Mar 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

I would be very cautious with the interpretation of cellular data generated with this compound. It is a urea with three aromatic elements and no real solubilizing group. While I have no solubility data in aqueous medium to share, I would be very surprised if this compound had a solubility profile suitable for a reliable cellular testing. The molecule was tested in-house in one cell-based assay, arguably not an optimal assay, but little activity has been observed which may well be the result of poor solubility and/or permeability.

(last updated: 31 Mar 2017 )

SERP Ratings

In Cell Rating

(last updated: 9 Apr 2017 )