Summary of Study ST001135

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000760. The data can be accessed directly via it's Project DOI: 10.21228/M8FH6C This work is supported by NIH grant, U2C- DK119886.

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Study IDST001135
Study TitleDifferent dose exposure of OPC-163493 on HepG2 cells (part-I)
Study TypeCompound dosage test
Study SummaryMetabolomics analysis were on 8 samples of HepG2 cells that were treated with compound OPC-163493 (DMSO control, 1, 3, or 10┬ÁM; each n=2) exposure for 30 min.
Institute
Otsuka Pharmaceutical Co., Ltd.
Last NameKanemoto
First NameNaohide
Address463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan
EmailKanemoto.Naohide@otsuka.jp
Phone81-03-6717-1400
Submit Date2019-02-07
Analysis Type DetailLC-MS
Release Date2019-03-06
Release Version1
Naohide Kanemoto Naohide Kanemoto
https://dx.doi.org/10.21228/M8FH6C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000760
Project DOI:doi: 10.21228/M8FH6C
Project Title:Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler
Project Summary:Inducing mitochondrial uncoupling (mUncoupling) is an attractive therapeutic strategy for treating metabolic diseases because it leads to calorie-wasting by reducing the efficiency of oxidative phosphorylation (OXPHOS) in mitochondria. Here we report a safe mUncoupler, OPC-163493, which has unique pharmacokinetic characteristics. OPC-163493 shows a good bioavailability upon oral administration and primarily distributed to specific organs: the liver and kidneys, avoiding systemic toxicities. It exhibitsinsulin-independent antidiabetic effects in multiple animal models of type I and type II diabetes and antisteatotic effects in fatty liver models. These beneficial effects can be explained by the improvement of glucose metabolism and enhancement of energy expenditure by OPC-163493 in the liver. Moreover, OPC-163493 treatment lowered blood pressure, extended survival, and improved renal function in the rat model of stroke/hypertension, possibly by enhancing NO bioavailability in blood vessels and reducing mitochondrial ROS production. OPC-163493 is a liver-localized/targeted mUncoupler that ameliorates various complications of diabetes.
Institute:Otsuka Pharmaceutical Co., Ltd.
Last Name:Kanemoto
First Name:Naohide
Address:463-10 Kagasuno Kawauchi-cho, Tokushima, Tokusima, 770-0865, Japan
Email:Kanemoto.Naohide@otsuka.jp
Phone:+81-88-665-2126
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