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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, 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)

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Joel Rüegger

LAB HEAD: Mario van

PROVIDER: PXD054026 | Pride | 2025-04-08

REPOSITORIES: Pride

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			Action	DRS
	JR008_01.raw	Raw
	JR008_02.raw	Raw
	JR008_09.raw	Raw
	JR008_10.raw	Raw
	JR008_11.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 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.

2025-04-08 | PXD035544 | 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.

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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 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 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 selectivity testing of BTK inhibitors in HEK293T cells.

2025-04-08 | PXD035551 | 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 selectivity testing of BTK inhibitors in MV4-11 cells.

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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 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 selectivity testing of Midostaurin in MV4-11 cells.

2025-04-08 | PXD035549 | 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 selectivity testing of Midostaurin in HEK293T cells.

2025-04-08 | PXD035619 | 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.

2025-04-08 | PXD053911 | Pride

Establishing an activity-based protein profiling platform to screen in situ kinase inhibitor engagement

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 selectivity testing of Midostaurin in MV4-11 cells. (Phosphoproteomics)

2025-04-09 | PXD055387 | Pride

Chemical proteomics with novel fully functionalized fragments and stringent target prioritization identifies the glutathione-dependent isomerase GSTZ1 as a lung cancer target

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