ArticleACS chemical biology2012
A synthetic polyphosphoinositide headgroup surrogate in complex with SHIP2 provides a rationale for drug discovery.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Crystal structure of human INPP5K with an allosteric inhibitor reveals the structural basis for species specific potency.Scientific reports · 2026Article
- Discovery of aurones bearing two amine functionalities as SHIP2 inhibitors with insulin-sensitizing effect in rat myotubes.RSC medicinal chemistry · 2024Article
- Discovery of a novel SHIP1 agonist that promotes degradation of lipid-laden phagocytic cargo by microglia.iScience · 2022Article
- Binding of CaStructure (London, England : 1993) · 2021Article
- Allosteric Site on SHIP2 Identified Through Fluorescent Ligand Screening and Crystallography: A Potential New Target for Intervention.Journal of medicinal chemistry · 2021Article
- Targeting SHIP1 and SHIP2 in Cancer.Cancers · 2021Review
- Article
- Regioisomeric Family of Novel Fluorescent Substrates for SHIP2.ACS medicinal chemistry letters · 2020Article
- Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes.ACS omega · 2020Article
- Combining data integration and molecular dynamics for target identification in α-Synuclein-aggregating neurodegenerative diseases: Structural insights on Synaptojanin-1 (Synj1).Computational and structural biotechnology journal · 2020Article
- IRTKS Promotes Insulin Signaling Transduction through Inhibiting SHIP2 Phosphatase Activity.International journal of molecular sciences · 2019Article
- Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Solution structure of SHIP2 SH2 domain and its interaction with a phosphotyrosine peptide from c-MET.Archives of biochemistry and biophysics · 2018Article
- Article
- Structural basis for interdomain communication in SHIP2 providing high phosphatase activity.eLife · 2017Article
- Article
- The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry).Angewandte Chemie (International ed. in English) · 2016Review
- Article
- The structure of phosphoinositide phosphatases: Insights into substrate specificity and catalysis.Biochimica et biophysica acta · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Phosphoinositides regulate many cellular processes, and cellular levels are controlled by kinases and phosphatases. SHIP2 (SH2 (Src homology 2)-domain-containing inositol-phosphatase-2) plays a critical role in phosphoinositide signaling, cleaving the 5-phosphate from phosphatidylinositol 3,4,5-trisphosphate. SHIP2 is thought to be involved in type-2 diabetes and obesity, conditions that could therefore be open to pharmacological modulation of the enzyme. However, rational design of SHIP2 inhibitors has been limited by the absence of a high-resolution structure. Here, we present a 2.1 Å resolution crystal structure of the phosphatase domain of SHIP2 bound to the synthetic ligand biphenyl 2,3',4,5',6-pentakisphosphate (BiPh(2,3',4,5',6)P(5)). BiPh(2,3',4,5',6)P(5) is not a SHIP2 substrate but inhibits Ins(1,3,4,5)P(4) hydrolysis with an IC(50) of 24.8 ± 3.0 μM, (K(m) for Ins(1,3,4,5)P(4) is 215 ± 28 μM). Molecular dynamics simulations suggest that when BiPh(2,3',4,5',6)P(5) binds to SHIP2, a flexible loop folds over and encloses the ligand. Compounds targeting such a closed conformation might therefore deliver SHIP2-specific drugs.
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Registered trials
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.