Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes

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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

Title: Novel Sulfonanilide Inhibitors of SHIP2 Enhance Glucose Uptake into Cultured Myotubes
Author: Berg, Mika Erik Anthon; Naams, Jette-Britt; Hautala, Laura; Tolvanen, Tuomas; Ahonen, Jari; Lehtonen, Sanna; Wähälä, Kristiina
Contributor organization: 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
HUS Helsinki and Uusimaa Hospital District
Date: 2020-01-28
Language: eng
Number of pages: 9
Belongs to series: ACS Omega
ISSN: 2470-1343
DOI: https://doi.org/10.1021/acsomega.9b02944
URI: http://hdl.handle.net/10138/317780
Abstract: 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
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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