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 |
Subject:
Subject ID: | SU002317 |
Subject Type: | Cultured cells |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Genotype Strain: | HOG |
Gender: | Male |
Cell Strain Details: | Human oligodendroglioma cell line |
Cell Counts: | 500,000 |
Species Group: | Mammals |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Genotype | Treatment |
---|---|---|---|
SA212572 | ML-11_Negative | HOG EV | BAY2402234 |
SA212573 | ML-11_Positive | HOG EV | BAY2402234 |
SA212574 | ML-12_Positive | HOG EV | BAY2402234 |
SA212575 | ML-20_Positive | HOG EV | BAY2402234 |
SA212576 | ML-20_Negative | HOG EV | BAY2402234 |
SA212577 | ML-19_Negative | HOG EV | BAY2402234 |
SA212578 | ML-19_Positive | HOG EV | BAY2402234 |
SA212579 | ML-12_Negative | HOG EV | BAY2402234 |
SA212580 | ML-27_Negative | HOG EV | BAY2402234 |
SA212581 | ML-28_Negative | HOG EV | BAY2402234 |
SA212582 | ML-28_Positive | HOG EV | BAY2402234 |
SA212583 | ML-27_Positive | HOG EV | BAY2402234 |
SA212584 | ML-03_Negative | HOG EV | BAY2402234 |
SA212585 | ML-04_Positive | HOG EV | BAY2402234 |
SA212586 | ML-04_Negative | HOG EV | BAY2402234 |
SA212587 | ML-03_Positive | HOG EV | BAY2402234 |
SA212588 | ML-17_Positive | HOG EV | DMSO |
SA212589 | ML-18_Negative | HOG EV | DMSO |
SA212590 | ML-26_Negative | HOG EV | DMSO |
SA212591 | ML-26_Positive | HOG EV | DMSO |
SA212592 | ML-25_Positive | HOG EV | DMSO |
SA212593 | ML-25_Negative | HOG EV | DMSO |
SA212594 | ML-18_Positive | HOG EV | DMSO |
SA212595 | ML-17_Negative | HOG EV | DMSO |
SA212596 | ML-10_Positive | HOG EV | DMSO |
SA212597 | ML-02_Positive | HOG EV | DMSO |
SA212598 | ML-10_Negative | HOG EV | DMSO |
SA212599 | ML-09_Positive | HOG EV | DMSO |
SA212600 | ML-09_Negative | HOG EV | DMSO |
SA212601 | ML-01_Positive | HOG EV | DMSO |
SA212602 | ML-02_Negative | HOG EV | DMSO |
SA212603 | ML-01_Negative | HOG EV | DMSO |
SA212604 | ML-07_Negative | HOG R132H | BAY2402234 |
SA212605 | ML-24_Negative | HOG R132H | BAY2402234 |
SA212606 | ML-24_Positive | HOG R132H | BAY2402234 |
SA212607 | ML-32_Positive | HOG R132H | BAY2402234 |
SA212608 | ML-31_Negative | HOG R132H | BAY2402234 |
SA212609 | ML-31_Positive | HOG R132H | BAY2402234 |
SA212610 | ML-32_Negative | HOG R132H | BAY2402234 |
SA212611 | ML-23_Negative | HOG R132H | BAY2402234 |
SA212612 | ML-23_Positive | HOG R132H | BAY2402234 |
SA212613 | ML-16_Positive | HOG R132H | BAY2402234 |
SA212614 | ML-08_Positive | HOG R132H | BAY2402234 |
SA212615 | ML-16_Negative | HOG R132H | BAY2402234 |
SA212616 | ML-07_Positive | HOG R132H | BAY2402234 |
SA212617 | ML-08_Negative | HOG R132H | BAY2402234 |
SA212618 | ML-15_Positive | HOG R132H | BAY2402234 |
SA212619 | ML-15_Negative | HOG R132H | BAY2402234 |
SA212620 | ML-29_Negative | HOG R132H | DMSO |
SA212621 | ML-14_Negative | HOG R132H | DMSO |
SA212622 | ML-29_Positive | HOG R132H | DMSO |
SA212623 | ML-30_Positive | HOG R132H | DMSO |
SA212624 | ML-14_Positive | HOG R132H | DMSO |
SA212625 | ML-30_Negative | HOG R132H | DMSO |
SA212626 | ML-05_Negative | HOG R132H | DMSO |
SA212627 | ML-21_Negative | HOG R132H | DMSO |
SA212628 | ML-22_Positive | HOG R132H | DMSO |
SA212629 | ML-22_Negative | HOG R132H | DMSO |
SA212630 | ML-13_Negative | HOG R132H | DMSO |
SA212631 | ML-06_Positive | HOG R132H | DMSO |
SA212632 | ML-13_Positive | HOG R132H | DMSO |
SA212633 | ML-05_Positive | HOG R132H | DMSO |
SA212634 | ML-06_Negative | HOG R132H | DMSO |
SA212635 | ML-21_Positive | HOG R132H | DMSO |
SA212636 | Blank | N/A | N/A |
SA212637 | ML-33_Negative | Pooled Sample | N/A |
SA212638 | ML-33_Positive | Pooled Sample | N/A |
Showing results 1 to 67 of 67 |
Collection:
Collection ID: | CO002310 |
Collection Summary: | Cells were washed with ice-cold saline and snap frozen in liquid nitrogen. |
Sample Type: | Cultured cells |
Treatment:
Treatment ID: | TR002329 |
Treatment 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. |
Sample Preparation:
Sampleprep ID: | SP002323 |
Sampleprep Summary: | Metabolites were extracted in 80% methanol, vortexed for 20 min at 4°C, and centrifuged (21,100 × g for 10 min at 4°C). Metabolite samples were dried using a CentriVap (Labconco) or SpeedVac (Thermo Fisher) concentrator. Dried metabolites were resuspended in 40-50 µL 80% acetonitrile, vortexed for 20 min at 4°C, and centrifuged (21,100 × g for 10 min at 4°C). 10 µL was injected and analyzed with a Q-Exactive HF-X hybrid quadrupole-orbitrap mass spectrometer (Thermo Fisher) coupled to a Vanquish Flex UHPLC system (Thermo Fisher). |
Combined analysis:
Analysis ID | AN003640 | AN003641 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | HILIC | HILIC |
Chromatography system | Vanquish Flex UHPLC | Vanquish Flex UHPLC |
Column | Millipore ZIC-pHILIC | Millipore ZIC-pHILIC |
MS Type | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive HF-X Orbitrap | Thermo Q Exactive HF-X Orbitrap |
Ion Mode | POSITIVE | NEGATIVE |
Units | TIC-Corrected Peak Area | TIC-Corrected Peak Area |
Chromatography:
Chromatography ID: | CH002695 |
Chromatography Summary: | Chromatographic resolution of metabolites was achieved using on a Millipore ZIC-pHILIC column using a linear gradient of 10 mM ammonium formate pH 9.8 and acetonitrile. |
Instrument Name: | Vanquish Flex UHPLC |
Column Name: | Millipore ZIC-pHILIC |
Flow Gradient: | linear gradient of 10 mM ammonium formate pH 9.8 and acetonitrile |
Solvent A: | 100% water; 10 mM ammonium formate pH 9.8 |
Solvent B: | 100% acetonitrile |
Chromatography Type: | HILIC |
MS:
MS ID: | MS003391 |
Analysis ID: | AN003640 |
Instrument Name: | Thermo Q Exactive HF-X Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Spectra were acquired with a resolving power of 60,000 full width at half maximum (FWHM), a scan range set to 80–1,200 m/z, and polarity switching. Data-dependent MS/MS data was acquired on unlabeled pooled samples to confirm metabolite IDs when necessary. Peaks were integrated using El-Maven 0.12.0 software (Elucidata) or TraceFinder 5.1 SP2 software (Thermo Fisher). Total ion counts were quantified using Freestyle 1.7 SP1 software (Thermo Fisher). Peaks were normalized to total ion counts using the R statistical programming language. |
Ion Mode: | POSITIVE |
MS ID: | MS003392 |
Analysis ID: | AN003641 |
Instrument Name: | Thermo Q Exactive HF-X Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | Spectra were acquired with a resolving power of 60,000 full width at half maximum (FWHM), a scan range set to 80–1,200 m/z, and polarity switching. Data-dependent MS/MS data was acquired on unlabeled pooled samples to confirm metabolite IDs when necessary. Peaks were integrated using El-Maven 0.12.0 software (Elucidata) or TraceFinder 5.1 SP2 software (Thermo Fisher). Total ion counts were quantified using Freestyle 1.7 SP1 software (Thermo Fisher). Peaks were normalized to total ion counts using the R statistical programming language. |
Ion Mode: | NEGATIVE |