Summary of Study ST002011
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 PR001275. The data can be accessed directly via it's Project DOI: 10.21228/M8WX21 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 | ST002011 |
| Study Title | The anticancer human mTOR inhibitor MLN0128/Sapanisertib with potent multistage in vitro antiplasmodium activity and in vivo antimalarial efficacy in a humanised mouse model is an inhibitor of multiple Plasmodium falciparum kinases. |
| Study Summary | Here we interrogated the in vitro metabolic effects of 6 drugs using ultra-high performance liquid chromatography mass-spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several distinctions between compounds with polypharmacological effects. |
| Institute | Pennsylvania State University |
| Department | Department of Biochemistry and Molecular Biology |
| Last Name | Llinas |
| First Name | Manuel |
| Address | W126 Millenium Science Complex, University Park, PA 16802 |
| manuel@psu.edu | |
| Phone | 814-867-3527 |
| Submit Date | 2021-12-08 |
| Raw Data Available | Yes |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-11-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001275 |
| Project DOI: | doi: 10.21228/M8WX21 |
| Project Title: | The anticancer human mTOR inhibitor MLN0128/Sapanisertib with potent multistage in vitro antiplasmodium activity and in vivo antimalarial efficacy in a humanised mouse model is an inhibitor of multiple Plasmodium falciparum kinases. |
| Project Type: | Treatment 10xIC50 of Antimalarials |
| Project Summary: | Here we interrogated the in vitro metabolic effects of 6 drugs using ultra-high performance liquid chromatography mass-spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several distinctions between compounds with polypharmacological effects. |
| Institute: | Pennsylvania State University |
| Department: | Department of Biochemistry and Molecular Biology |
| Last Name: | Llinas |
| First Name: | Manuel |
| Address: | W126 Millenium Science Complex, University Park, PA 16802 |
| Email: | manuel@psu.edu |
| Phone: | 814-867-3527 |
Subject:
| Subject ID: | SU002092 |
| Subject Type: | Cultured cells |
| Subject Species: | Plasmodium falciparum |
| Taxonomy ID: | 5833 |
| Genotype Strain: | 3D7 |
Factors:
Subject type: Cultured cells; Subject species: Plasmodium falciparum (Factor headings shown in green)
| mb_sample_id | local_sample_id | Concentration | Treatment time | Parasite Stage |
|---|---|---|---|---|
| SA188316 | ATQ1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188317 | MMV652103_1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188318 | MMV030084-3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188319 | MMV652103_3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188320 | MMV1900328_1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188321 | MMV1900328_3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188322 | MMV1900328_2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188323 | MMV030084-2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188324 | MMV652103_2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188325 | ATQ3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188326 | MMV030084-1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188327 | ATQ2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188328 | MLN1028_2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188329 | MLN1028_1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188330 | KAI407-3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188331 | MLN1028_3 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188332 | KAI407-2 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188333 | KAI407-1 | 10X IC50 | 2.5 hours | MACS purified Troph |
| SA188334 | Blank1 | N/A | N/A | MACS purified Troph |
| SA188335 | Blank2 | N/A | N/A | MACS purified Troph |
| SA188336 | Blank3 | N/A | N/A | MACS purified Troph |
| SA188337 | Pool3 | N/A | N/A | MACS purified Troph |
| SA188338 | ND1 | N/A | N/A | MACS purified Troph |
| SA188339 | ND2 | N/A | N/A | MACS purified Troph |
| SA188340 | ND3 | N/A | N/A | MACS purified Troph |
| SA188341 | Pool1 | N/A | N/A | MACS purified Troph |
| SA188342 | Pool2 | N/A | N/A | MACS purified Troph |
| Showing results 1 to 27 of 27 |
Collection:
| Collection ID: | CO002085 |
| Collection Summary: | Cells were pelleted and the media aspirated then a 1xPBS wash that was aspirated prior to quench and extraction. |
| Sample Type: | Pf infected RBCs |
Treatment:
| Treatment ID: | TR002104 |
| Treatment Summary: | Purified iRBCs were treated with 10XIC50 drug for 2.5 hours |
Sample Preparation:
| Sampleprep ID: | SP002098 |
| Sampleprep Summary: | 90% Methanol/10% water at 50:1 solvent/cell pellet followed by vortexing and clarification via centrifugation. |
| Processing Method: | Lysis |
| Processing Storage Conditions: | 4? |
| Extraction Method: | See SA Cobbold et al JBC 2013 |
| Extract Cleanup: | Clarification via centrifugation followed by nitrogen drying |
| Extract Storage: | -80? |
| Sample Spiking: | Internal Standard 13C4, 15N1-Aspartate used for sample preparation normalizer |
Combined analysis:
| Analysis ID | AN003277 | AN003278 | AN003279 |
|---|---|---|---|
| Analysis type | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 RS | Thermo Dionex Ultimate 3000 RS | Thermo Dionex Ultimate 3000 RS |
| Column | Waters XSelect HSS T3 C18 (100 x 2.1mm,2.5um) | Water XSelect HSS T3 C18 (100 x 2.1mm,2.5um) | Water XSelect HSS T3 C18 (100 x 2.1mm,2.5um) |
| MS Type | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Exactive Plus Orbitrap | Thermo Exactive Plus Orbitrap | Thermo Exactive Plus Orbitrap |
| Ion Mode | NEGATIVE | NEGATIVE | NEGATIVE |
| Units | peak area | peak area | peak area |
Chromatography:
| Chromatography ID: | CH002419 |
| Instrument Name: | Thermo Dionex Ultimate 3000 RS |
| Column Name: | Waters XSelect HSS T3 C18 (100 x 2.1mm,2.5um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH002420 |
| Instrument Name: | Thermo Dionex Ultimate 3000 RS |
| Column Name: | Water XSelect HSS T3 C18 (100 x 2.1mm,2.5um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH002421 |
| Instrument Name: | Thermo Dionex Ultimate 3000 RS |
| Column Name: | Water XSelect HSS T3 C18 (100 x 2.1mm,2.5um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS003049 |
| Analysis ID: | AN003277 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | El-Maven for feature assignments |
| Ion Mode: | NEGATIVE |
| MS ID: | MS003050 |
| Analysis ID: | AN003278 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | El-Maven for feature assignments |
| Ion Mode: | NEGATIVE |
| MS ID: | MS003051 |
| Analysis ID: | AN003279 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | El-Maven for feature assignments |
| Ion Mode: | NEGATIVE |
