Evidence map›Paper›PMID 39693863›Full record

ArticleEuropean journal of medicinal chemistry2025

Structure-activity relationship studies and design of a PTPN22 inhibitor with enhanced isozyme selectivity and cellular efficacy.

Brenson A Jassim, Yunpeng Bai, Zihan Qu, Conrad J Sander, Jianping Lin, Jinmin Miao, Zhong-Yin Zhang

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Article in European journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Brenson A JassimBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Yunpeng BaiBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Zihan QuJames Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Conrad J SanderBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Jianping LinBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Jinmin MiaoBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Zhong-Yin ZhangBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA; Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: zhang-zy@purdue.edu.

Funding

Structure/Function of Protein Tyrosine PhosphatasesR01CA069202 · NCI · YESHIVA UNIVERSITY · PI Zhong-Yin Zhang · 1996 to 2026
$7.3M
NCI NIH HHS R01 CA069202
6 · The paper itself

Abstract

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) lies downstream of the T cell receptor (TCR) and attenuates T cell signaling by dephosphorylating key effector proteins such as LCK, Zap70, and the intracellular region of the TCR. Recent evidence implicates PTPN22 as an exciting target for enabling immunotherapeutic efficacy against cancer. We carried out structural optimization of a benzofuran salicylic acid-based orthosteric PTPN22 inhibitor 8b, using a combination of crystal structure analysis, synthesis, matched molecular pairs analysis, and biochemical and cell-based assays. Herein, we report structure-activity relationship studies, lead optimization based on the 8b-PTPN22 co-crystal structure, and cellular evaluation of the top analog. Notably, our efforts yielded compound 8b-19, an essentially equipotent scaffold with superior isozyme selectivity, improved aqueous solubility, and significantly enhanced cellular efficacy compared to the parent 8b. This compound may serve as a lead for further optimization of PTPN22-targeting immunotherapies or as a chemical probe for interrogation for additional links between PTPN22 and immunomodulation in cells.

Indexed as

Drug DesignEnzyme InhibitorsIsoenzymesProtein Tyrosine Phosphatase, Non-Receptor Type 22Dose-Response Relationship, DrugHumansModels, MolecularMolecular StructureStructure-Activity RelationshipEnzyme InhibitorsIsoenzymesProtein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, humanCancer immunotherapyLYPPTPN22PTPN22 inhibitors

Identifiers

PMID39693863
PMCPMC11709133

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.