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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001135 |
| Study Title | Different dose exposure of OPC-163493 on HepG2 cells (part-I) |
| Study Type | Compound dosage test |
| Study Summary | Metabolomics analysis were on 8 samples of HepG2 cells that were treated with compound OPC-163493 (DMSO control, 1, 3, or 10µM; each n=2) exposure for 30 min. |
| Institute | Otsuka Pharmaceutical Co., Ltd. |
| Last Name | Kanemoto |
| First Name | Naohide |
| Address | 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan |
| Kanemoto.Naohide@otsuka.jp | |
| Phone | 81-03-6717-1400 |
| Submit Date | 2019-02-07 |
| Analysis Type Detail | LC-MS |
| Release Date | 2019-03-06 |
| Release Version | 1 |
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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 |
Subject:
| Subject ID: | SU001196 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Gender: | Not applicable |
| Cell Strain Details: | HepG2 cells |
| Species Group: | Mammals |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA078229 | OPC-0uM-5 | - |
| SA078230 | OPC-0uM-1 | - |
| SA078231 | OPC-1uM-2 | 1 |
| SA078232 | OPC-1uM-6 | 1 |
| SA078235 | OPC-10uM-8 | 10 |
| SA078236 | OPC-10uM-4 | 10 |
| SA078233 | OPC-3uM-3 | 3 |
| SA078234 | OPC-3uM-7 | 3 |
| Showing results 1 to 8 of 8 |
Collection:
| Collection ID: | CO001190 |
| Collection Summary: | Culture medium of HepG2 cells in 100-mm dish was aspirated and cells were washed twice by 5% mannitol solution, and then processed with sampleprep steps. |
| Sample Type: | HepG2 cells |
| Storage Conditions: | Room temperature |
Treatment:
| Treatment ID: | TR001211 |
| Treatment Summary: | HepG2 cells were seeded into a 100mm dish the day before OPC-163493 treatment. OPC-163493 treatments (DMSO control, 1, 3, or 10uM, each n=2) were performed for 30min in FBS-free DMEM with high glucose (25mM). |
| Treatment Dose: | 0uM, 1uM, 3uM, 10uM |
| Treatment Doseduration: | 30 min |
| Cell Media: | MEM with Earle`s salts, L-Glutamine and Non-Essiontial Amino Acids, 10% fetal bovine serum, and 1mM sodium pyruvate solution |
Sample Preparation:
| Sampleprep ID: | SP001204 |
| Sampleprep Summary: | Culture medium of HepG2 cells in 100-mm dish was aspirated and cells were washed twice by 5% mannitol solution, and then the cells were treated with methanol. The cell extract was treated with Mili-Q water containing internal standard and filtered with 5-kDa cutoff filter. The filtrate was centrifugally concentrated and re-suspended in 50 µL of Milli-Q water. |
| Processing Storage Conditions: | Room temperature |
| Extract Storage: | -80℃ |
| Sample Resuspension: | 50 uL Mili-Q |
Chromatography:
| Chromatography ID: | CH001347 |
| Chromatography Summary: | capillary electrophoresis was connected with time-of-flight mass spectrometry (CE-TOFMS) for cation analysis and tandem mass spectrometry (CE-MS/MS) for anion. |
| Instrument Name: | Agilent 7100 CE |
| Column Name: | Fused silica capillary, i.d. 50 μm × 80 cm |
| Chromatography Type: | CE |
Analysis:
| Analysis ID: | AN001860 |
| Analysis Type: | MS |
| Chromatography ID: | CH001347 |
| Num Factors: | 4 |
| Num Metabolites: | 48 |
| Units: | Concentration (pmol/1000000 cells) |
| Analysis ID: | AN001861 |
| Analysis Type: | MS |
| Chromatography ID: | CH001347 |
| Num Factors: | 4 |
| Num Metabolites: | 56 |
| Units: | Concentration (pmol/1000000 cells) |
