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CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

ABSTRACT: Activity-based protein profiling is a powerful tool to study target engagement in complex biological environments. XO44 is a chemical probe based on the scaffold of a promiscuous kinase binder, which covalently reacts with a conserved lysine in the ATP-binding pocket of kinases. Pretreatment of cells with a drug (candidate) results in competition of XO44 binding, which can be interpreted as in situ target engagement. Here, a workflow is presented which is optimized for kinome coverage, reproducibility and data processing. This dataset pertains to the kinome coverage of XO44 in 19 human cell lines as determined by chemical proteomics.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Joel Rüegger

LAB HEAD: Mario van

PROVIDER: PXD035544 | Pride | 2025-04-08

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	A375_DMSO.raw	Raw
	A375_XO44_1.raw	Raw
	A375_XO44_2.raw	Raw
	A375_XO44_3.raw	Raw
	AMO1_DMSO.raw	Raw

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CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

Project description:Activity-based protein profiling is a powerful tool to study target engagement in complex biological environments. XO44, ALX005 and ALX011 are chemical probes based on the scaffold of a promiscuous kinase binder, which covalently reacts with a conserved lysine in the ATP-binding pocket of kinases. Pretreatment of cells with a drug (candidate) results in competition of XO44/ALX005/ALX011 binding, which can be interpreted as in situ target engagement. Here CellEKT is presented, a workflow which is optimized for kinome coverage, reproducibility and data processing. This dataset contains the kinome coverage assessment of ALX005 and ALX011 in comparison to the kinome coverage of XO44 which was determined in the selectivity screening of Midostaurin (PXD035619, PXD035549)

2025-04-08 | PXD054026 | Pride

CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

Project description:Activity-based protein profiling is a powerful tool to study target engagement in complex biological environments. XO44 is a chemical probe based on the scaffold of a promiscuous kinase binder, which covalently reacts with a conserved lysine in the ATP-binding pocket of kinases. Pretreatment of cells with a drug (candidate) results in competition of XO44 binding, which can be interpreted as in situ target engagement. Here, a workflow is presented which is optimized for kinome coverage, reproducibility and data processing. This dataset pertains to the difference in kinome coverage when using different protocols and (strept)avidin beads.

2025-04-08 | PXD035542 | Pride

CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

Project description:Activity-based protein profiling is a powerful tool to study target engagement in complex biological environments. XO44 is a chemical probe based on the scaffold of a promiscuous kinase binder, which covalently reacts with a conserved lysine in the ATP-binding pocket of kinases. Pretreatment of cells with a drug (candidate) results in competition of XO44 binding, which can be interpreted as in situ target engagement. Here, a workflow is presented which is optimized for kinome coverage, reproducibility and automated data processing. This dataset pertains to the use of high probe dose samples as peptide library in MaxQuant.

2025-04-08 | PXD035540 | Pride

CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

Project description:Activity-based protein profiling is a powerful tool to study target engagement in complex biological environments. XO44, ALX005 and ALX011 are chemical probes based on the scaffold of a promiscuous kinase binder, which covalently reacts with a conserved lysine in the ATP-binding pocket of kinases. Pretreatment of cells with a drug (candidate) results in competition of XO44/ALX005/ALX011 binding, which can be interpreted as in situ target engagement. Here CellEKT is presented, a workflow which is optimized for kinome coverage, reproducibility and data processing. This dataset pertains to the selectivity testing of Dasatinib in MV4-11 cells using a probe cocktail of XO44, ALX005 and ALX011.

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CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

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CellEKT: A chemical proteomics assay to profile cellular target engagement of kinase inhibitors

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