Dataset Information

Identifying Drug Targets with Thermal Proteome Profiling using IBT-16plex

ABSTRACT: Application of 16-plex iBT to drug target identification

ORGANISM(S): Homo Sapiens

SUBMITTER: Piliang Hao

PROVIDER: PXD041275 | iProX | Thu Mar 30 00:00:00 BST 2023

REPOSITORIES: iProX

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Identifying drug targets with thermal proteome profiling using IBT-16plex.

Shi Zhaomei Z Ren Yan Y Li Shuwei S Hao Piliang P

Rapid communications in mass spectrometry : RCM 20240101 1

<h4>Rationale</h4>Thermal proteome profiling (TPP) has been widely used for the identification of drug targets for several years, and TMTpro-16plex has recently been evaluated for TPP of vehicle- and drug-treated samples in a single labeling process to reduce missing values and save instrument time. A novel isobaric labeling reagent, IBT-16plex, was developed with slightly better performance in protein identification and quantification than the commercially available TMTpro-16plex.<h4>Methods</h ...[more]

PMID: 38073198

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Project description:The FITExP profiling approach was used to identify protein hits from cells incubated with RAPTA-T or RAPTA-EA. Validation experiments with paclitaxel and cisplatin underlined the reliability of the method and hit lists for both test compounds (and?) gave physiologically viable anti-cancer mechanisms. The hit proteins for paclitaxel match with those published and the ones obtained for cisplatin were related to DNA repair, which is in line with the principal mechanism of cisplatin cytotoxicity involving the formation of nuclear DNA lesions. RAPTA-T treatment leads to upregulation of multiple hits suggesting a broad mechanism of action involving both metastasis and tumorigenicity. In contrast, hit proteins identified after incubation with RAPTA-EA are linked to regulation of the oxidative stress response and are therefore thought to be conferred by the EA moiety in the drug. From a therapeutic standpoint, RAPTA-EA could be explored in cancers where EA alone has shown potency, such as chronic lymphocytic leukemias,91 or where EA combined with another agent shows synergy, such as the combination of EA with afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitors for breast cancers.92 On the other hand, due to its broad mechanism of action, RAPTA-T could potentially be more useful if used concomitantly with drugs that target specific cancer pathways and could also play a role in therapies for later stage cancers due to its anti-metastatic properties. Here, application of the FITExP allowed us to gauge the mechanistic pathways involved in the action of two novel ruthenium(II) metallodrugs with very different phenotypic characteristics and from this knowledge infer their role in therapy. Potentially, future application of the FITExP approach in this manner could be useful for identification of cancer chemotherapy drug combinations, where commonly cancer clinical trials fail at phase II where drug combinations are first tried and tested.

Dataset Information

Identifying Drug Targets with Thermal Proteome Profiling using IBT-16plex

Publications

Identifying drug targets with thermal proteome profiling using IBT-16plex.

Similar Datasets

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