Summary of Study ST002231
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 PR001421. The data can be accessed directly via it's Project DOI: 10.21228/M81X41 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002231 |
| Study Title | Metabolomics Analysis of HOG-EV and HOG-R132H Cells with and without BAY 2402234 Treatment |
| Study Type | Metabolomics Analysis |
| Study Summary | HOG cells were plated in 6-well plates (0.5 × 10^6 cells per well). 24 hours later, HOG-EV or HOG-R132H cells were treated for 24 hours with 10 nM BAY 2402234 or DMSO. Cells were then harvested for LC-MS analysis. |
| Institute | UT Southwestern Medical Center |
| Department | Children's Research Institute |
| Laboratory | McBrayer Laboratory |
| Last Name | McBrayer |
| First Name | Samuel |
| Address | 6000 Harry Hines Boulevard, NL10.110K, Dallas, TX 75235, USA |
| samuel.mcbrayer@utsouthwestern.edu | |
| Phone | (214)-648-3730 |
| Submit Date | 2022-07-14 |
| Num Groups | 4 |
| Total Subjects | 1 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-07-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001421 |
| Project DOI: | doi: 10.21228/M81X41 |
| Project Title: | De Novo Pyrimidine Synthesis is a Targetable Vulnerability in IDH Mutant Glioma |
| Project Type: | LC-MS Quantitative Analysis |
| Project Summary: | Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they appear less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1 mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH mutant gliomas. Mechanistically, this reflects an obligate dependence of glioma cells on the de novo pyrimidine synthesis pathway and mutant IDH’s ability to sensitize to DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation. |
| Institute: | UT Southwestern Medical Center |
| Department: | Children's Research Institute |
| Laboratory: | McBrayer Laboratory |
| Last Name: | McBrayer |
| First Name: | Samuel |
| Address: | 6000 Harry Hines Boulevard, NL11.110K, Dallas, Texas, 75235, USA |
| Email: | samuel.mcbrayer@utsouthwestern.edu |
| Phone: | (214)-648-3730 |
