ABL127

ABL127 : Covalent Inhibitor of PPME1

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe ABL127 is in the process of SERP review.

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Information

PPME1

Covalent Inhibitor

100 nM, up to 10 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9Y570

Target Class: Enzyme

Target SubClass: Serine hydrolase

Potency: IC50

Potency Value: 4.2 nM

Potency Assay: Gel-based competitive ABPP with FP-Rh (2 μM) in the soluble proteome (1 mg/mL protein) of MDA-MB-231 cells.

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

Target aliases:

Protein phosphatase methylesterase 1, PME1, PPME1, ...

DOI Reference: 10.1073/pnas.1015248108

Uniprot ID: Q9Y570

Target Class: Enzyme

Target SubClass: Serine hydrolase

Potency: INH

Potency Value: 500 nM

Potency Assay: inhibition of demethylated PP2A using Western of lysate of HEK293T cells spiked with recombinant PME-1

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

Target aliases:

Protein phosphatase methylesterase 1, PME1, PPME1, ...

DOI Reference: 10.1073/pnas.1015248108

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): Combined mass spec LC revealed complete and selective in situ inhibition of PME-1 by ABL127 with no activity against > 50 other serine hydrolases detected in MDA-MB-231 and HEK 293T cells.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

ABL127 is a highly potent PME1 inhibitor (apparent IC50 ~10 nM in cells). Treatment with ABL127 affords a partial decrease in PPME1 methylation. ~100 nM recommended dose for cell based studies, with off target activity against several serine hydrolases expected above 1uM dose. In model organism (mouse) studies require high dose (50 mg/kg) to achieve target engagement, which may reflect metabolic instability.

(last updated: 18 Nov 2023 )