ABBV-CLS-484

ABBV-CLS-484 : Competitive, reversible of PTPN2, PTPN1

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 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 ABBV-CLS-484 is in the process of SERP review.

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Information

PTPN2
PTPN1

Competitive, reversible

up to 1 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P17706

Target Class: Enzyme

Target SubClass: Phosphatase

Potency: IC50

Potency Value: 1.8 nM

Potency Assay: Mobility shift assay

PDB ID for probe-target interaction (3D structure): 7UAD

Target aliases:

Tyrosine-protein phosphatase non-receptor type 2, ...

DOI Reference: 10.1038/s41586-023-06575-7

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Off Target: PTPN9

Potency end-point : IC50 15 nM

Potency assay (off target): In a biochemical phosphatase screen, AC484 demonstrated high selectivity for PTPN2/N1, with 6–8-fold weaker activity on PTPN9 and no detectable activity on SHP-1 or SHP-2. Furthermore, wide-range selectivity screens across a diverse panel of phosphatases, kinases and other receptors, including the hERG channel, showed no off-target activity of AC484.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

A concentration of 1 uM seems sufficient to achieve full response in cells using multiple readouts. Of note, no data regarding cellular toxicity at that concentration have been shown. If used in whole blood, concentrations above 10 uM seem to be required to achieve full response (STAT5 phosphorylation, IFNg and TNF readouts). While a dose of 100 mg/kg twice daily was not tolerated in some animals, 150 mg/kg daily was tolerated and doses up to 100 mg/kg daily were required in tumor challenge experiments. For that reason, I would recommend a dose of 100 mg/kg daily to achieve a high and well tolerated compound exposure.

(last updated: 3 Jan 2024 )