OSMI-4

OSMI-4 : Inhibitor of OGT

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe OSMI-4 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

Inhibitor

up to 10 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: O15294

Target Class: Enzyme

Target SubClass: Glycosyltransferase

Potency: Kd

Potency Value: 8 nM

Potency Assay: MST (microscale thermophoresis) of active form 4a

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

Target aliases:

UDP-N-acetylglucosamine--peptide N-acetylglucosami ...

DOI Reference: 10.1021/jacs.8b07328

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): Proteomics after treatment with 20 uM of HEK293T cells shows significant changes in abundance for XBP and other proteins related to ER stress.

I have extra information to add

SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The proposed binding mode is well in line with the biochemical data. The compound is very potent in MST binding assay, but the potency does not translate to cellular activity with EC50 of 3 uM. A selectivity assay such as a pulldown proteomics would be desirable. For this compound a negative probe is missing. Evaluation of the enantiomer for OSMI-4 which was shown for the other compounds OSMI-2 and OSMI-3 could potentially provide a negative control compound. There are no signs of general cytotoxicity. Western blot of OSMI3 (2b) and OSMI4 (4b) shows deviating density in uncleaved HCF-1 cells indicating different concentrations.

(last updated: 23 Sept 2024 )