Evidence map›Paper›PMID 39454561›Full record

ArticleBioorganic & medicinal chemistry2024

Discovery and evaluation of novel SHIP-1 inhibitors.

Jinmin Miao, Jianping Lin, Jiajun Dong, Ovini Amarasinghe, Emily R Mason, Shaoyou Chu, Zihan Qu, Clayton C Cullers, Karson S Putt, Zhong-Yin Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
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

10 authors.

Jinmin MiaoBorch 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.
Jiajun DongBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Ovini AmarasingheBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Emily R MasonDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Shaoyou ChuDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Zihan QuDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Clayton C CullersDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Karson S PuttInstitute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA.
Zhong-Yin ZhangBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA; Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA. Electronic address: zhang-zy@purdue.edu.

Funding

Structural Biology CoreU54AG065181 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Alan D. Palkowitz · 2019 to 2026
$61.3M
Structure/Function of Protein Tyrosine PhosphatasesR01CA069202 · NCI · YESHIVA UNIVERSITY · PI Zhong-Yin Zhang · 1996 to 2026
$7.3M
NCI NIH HHS R01 CA069202NIA NIH HHS U54 AG065181
6 · The paper itself

Abstract

Src Homology 2-containing Inositol 5'-Phosphatase-1 (SHIP-1), encoded by INPP5D, has been identified as an Alzheimer's disease (AD) risk-associated gene through recent genetic and epigenetic studies. SHIP-1 confers AD risk by inhibiting the TREM2 cascade and reducing beneficial microglial cellular processes, including phagocytosis. While several small molecules have been reported to modulate SHIP-1 activity, their limited selectivity and efficacy in advanced models restricted their potential as therapeutic agents or probes for biological studies. Herein, we validated and implemented a high-throughput screening platform to explore new chemotypes that can modulate the phosphatase activity of SHIP-1. We screened 49,260 central nervous system (CNS)-penetrate compounds sourced from commercial vendors using the malachite green-based assay for anti-SHIP-1 activity. Through analysis, prioritization, and validation of the screening hits, we identified three novel types of scaffolds that inhibit the SHIP-1 phosphatase activity with IC

Indexed as

Drug DiscoveryEnzyme InhibitorsPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesDose-Response Relationship, DrugHigh-Throughput Screening AssaysHumansMolecular StructureStructure-Activity RelationshipEnzyme InhibitorsINPP5D protein, humanPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesAlzheimer’s diseaseHigh-throughput screeningMicroglial phagocytosisSrc Homology 2-containing Inositol 5′-Phosphatase-1 (SHIP-1)

Identifiers

PMID39454561
PMCPMC11551725

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Registered trials

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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 OpenQuestion graph.