Dataset Information

Affinity-based chemoproteomic profiling of UNC0638 and UNC0737 in MCF7 and PBMC lysates identifies CHKA as a shared off-target.

ABSTRACT: To identify the molecular target(s) and elucidate the mechanism of action of UNC0638 and UNC0737, affinity-based chemoproteomics was performed. UNC0965, a biotinylated analogue of UNC0638, was immobilised on streptavidin-coated sepharose beads to enrich binding proteins from whole MCF7 or PBMC cell lysates. UNC0636 or UNC0737 were added as competitors in control experiments to identify specific binders.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Breast, Breast Adenocarcinoma Cell Line, Blood

SUBMITTER: Ludwig Bauer

LAB HEAD: Kilian Huber

PROVIDER: PXD056865 | Pride | 2025-01-27

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	QE772_MSQ1022_20170428_JAW_009_PMBC_61_UNC0638_1.raw	Raw
	QE772_MSQ1022_20170428_JAW_009_PMBC_62_UNC0638_2.raw	Raw
	QE772_MSQ1022_20170428_JAW_009_PMBC_71_UNC0737_1.raw	Raw
	QE772_MSQ1022_20170428_JAW_009_PMBC_72_UNC0737_2.raw	Raw
	QE772_MSQ1022_20170428_JAW_009_PMBC_D1_DMSO_1.raw	Raw

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Publications

Phenomics-Based Discovery of Novel Orthosteric Choline Kinase Inhibitors.

Bauer Ludwig G LG Ward Jennifer A JA Díaz-Sáez Laura L Sundström Yvonne Y Tolvanen Tuomas T Alarcón Barrera Juan Carlos JC Kostidis Sarantos S Rogers Catherine M CM Panagakou Ioanna I Singh Usha U Rothweiler Elisabeth M EM Gonzalez Orta Alejandro A Kaniskan H Ümit HÜ Hu Jianping J Jin Jian J Sievers Sonja S Waldmann Herbert H Giera Martin M Sundström Michael M Berg Louise L Huber Kilian V M KVM

Angewandte Chemie (International ed. in English) 20241230

Choline kinase alpha (CHKA) is a central mediator of cell metabolism linked to cancer and immune regulation. Cellular and clinical evaluation of CHKA has been hampered by challenges in the development of drug-like choline kinase inhibitors. Here, we identify CHKA as an unexpected off-target of histone methyltransferase inhibitors using an integrated phenomic approach. We confirm CHKA as a direct protein target of the aminoquinazolines UNC0638 and UNC0737 using a combination of chemoproteomic, bi ...[more]

PMID: 39740997

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