BI-4916

BI-4916 : Inhibitor Prodrug of PHGDH

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe BI-4916 is in the process of SERP review.

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Information

PHGDH

Prodrug

up to 10 uM

In Vitro Validations

Uniprot ID: O43175

Target Class: Enzyme

Target SubClass: Dehydrogenase

Potency: IC50

Potency Value: 3 nM

Potency Assay: Biochemical Assay performed with the active form BI-4924

PDB ID for probe-target interaction (3D structure): 6RJ6

Target aliases:

D-3-phosphoglycerate dehydrogenase, PGDH3, PHGDH, ...

DOI Reference: 10.1021/acs.jmedchem.9b00718

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): MDA-MB-468 cell extracts in the presence or absence of 10 μM BI-4924 were used for identification and quantitative comparison in LC–tandem mass spectrometry (MS/MS). Analysis revealed a clean selectivity profile for BI-4924. Of the 31 dehydrogenases in the data set, only alcohol dehydrogenase class-3 and 3-hydroxyisobutyrate dehydrogenase were identified as off targets.

Probe Selectivity in Vitro:

CEREP counterscreen panel (4/40 offtargets >50% inhibition @ 10 μM

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

BI-4916 is a ethyl ester prodrug of the active (carboxylic acid) component BI-4943, with intracellular ester cleavage demonstrated and accumulation of the active drug component in MDA-MB-468 cells quantified, along with evidence of intracellular target engagement and time dependent cellular enrichment of the active (carboxylic acid) component BI-4943. BI-4924 has a comprehensive data package and exhibits a good selectivity profile evaluate via chemical proteomics (2/31 dehydrogenases) as well as in a CEREP counterscreen panel (4/40 offtargets >50% inhibition @ 10µM).

(last updated: 12 Feb 2025 )