Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes

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http://hdl.handle.net/10138/317780

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Berg , M E A , Naams , J-B , Hautala , L , Tolvanen , T , Ahonen , J , Lehtonen , S & Wähälä , K 2020 , ' Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes ' , ACS Omega , vol. 5 , no. 3 , pp. 1430-1438 . https://doi.org/10.1021/acsomega.9b02944

Titel: Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes
Författare: Berg, Mika Erik Anthon; Naams, Jette-Britt; Hautala, Laura; Tolvanen, Tuomas; Ahonen, Jari; Lehtonen, Sanna; Wähälä, Kristiina
Upphovmannens organisation: Research Services
Doctoral Programme in Chemistry and Molecular Sciences
Department of Chemistry
Diabetes and Obesity Research Program
Doctoral Programme in Biomedicine
Sanna Lehtonen research group
Doctoral Programme in Integrative Life Science
Department of Pathology
Doctoral Programme in Drug Research
Medicum
Datum: 2020-01-28
Språk: eng
Sidantal: 9
Tillhör serie: ACS Omega
ISSN: 2470-1343
DOI: https://doi.org/10.1021/acsomega.9b02944
Permanenta länken (URI): http://hdl.handle.net/10138/317780
Abstrakt: A series of substituted sulfonanilide analogs were prepared and evaluated as novel potent inhibitors of SH2 domaincontaining inositol polyphosphate 5′-phosphatase 2 (SHIP2). SHIP2 has been shown to be a new attractive target for the treatment of insulin resistance in type 2 diabetes mellitus (T2D), which can lead to life-threatening diabetic kidney disease (DKD). Amongst the synthesized compounds, the two most promising candidates, 10 and 11, inhibited SHIP2 significantly. Additionally, these compounds induced Akt activation in a dose-dependent manner, increased the presence of glucose transporter 4 at the plasma membrane, and enhanced glucose uptake in cultured myotubes in vitro at lower concentrations than metformin, the most widely used antidiabetic drug. These results show that the novel SHIP2 inhibitors have insulin sensitizing capacity and provide prototypes for further drug development for T2D and DKD.
Subject: 5'-PHOSPHATASE-2 GENE POLYMORPHISMS
ASSOCIATION
CELLS
INOSITOL
INPPL1
METFORMIN
PHOSPHATASE
PLASMA-MEMBRANE
STIMULATION
SULFONYLUREAS
116 Chemical sciences
3121 General medicine, internal medicine and other clinical medicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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