Dataset Information

Selectivity profiling of inhibitor treated human cells via full proteome profiling

ABSTRACT: Three selective hit compounds from an arrayed kinome abundance screen (98 kinases vs 1570 kinase inhibitors) were subjected to full proteome profiling by TMTpro 18-plex to assess their degradation selectivity in K562 cells. Src inhibitor 3 showed the most significant downregulation of the target kinase LYN. TAK285 did not significantly affect any kinase. Finally, CSK and RIPK2 (drug screen targets) were identified as the only two kinase targets downregulated by RIPK-IN-4. The compounds were further assessed for their detailed mode of action as reported with orthogonal assays such as FACS-based CRISPR/Cas9 screens and BioID.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Fabian Frommelt

LAB HEAD: Georg E. Winter

PROVIDER: PXD053130 | Pride | 2025-06-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CC_GW_174.pdStudy	Other
	CC_GW_174_P13033_M1160-1.raw	Raw
	CC_GW_174_P13033_M1160-10.raw	Raw
	CC_GW_174_P13033_M1160-11.raw	Raw
	CC_GW_174_P13033_M1160-12.raw	Raw

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Publications

Inhibitors supercharge kinase turnover through native proteolytic circuits.

Scholes Natalie S NS Bertoni Martino M Comajuncosa-Creus Arnau A Kladnik Katharina K Guo Xuefei X Frommelt Fabian F Hinterndorfer Matthias M Razumkov Hlib H Prokofeva Polina P Schwalm Martin P MP Born Florian F Roehm Sandra S Imrichova Hana H Santini Brianda L BL Barone Eleonora E Schätz Caroline C Muñoz I Ordoño Miquel M Lechner Severin S Rukavina Andrea A Serrano Iciar I Abele Miriam M Koren Anna A Kubicek Stefan S Knapp Stefan S Gray Nathanael S NS Superti-Furga Giulio G Kuster Bernhard B Shi Yigong Y Aloy Patrick P Winter Georg E GE

Nature 20251126 8098

Targeted protein degradation is a pharmacological strategy that relies on small molecules such as proteolysis-targeting chimeras (PROTACs) or molecular glues, which induce proximity between a target protein and an E3 ubiquitin ligase to prompt target ubiquitination and proteasomal degradation<sup>1</sup>. Sporadic reports indicated that ligands designed to inhibit a target can also induce its destabilization<sup>2-4</sup>. Among others, this has repeatedly been observed for kinase inhibitors<sup ...[more]

PMID: 41299171

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