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Phosphoproteomic profiling of WNTinib

ABSTRACT: Phosphoproteome profiling small molecule on sensitive and insensitive murineHCC tumour organoids

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Ernesto Guccione

PROVIDER: PXD024958 | JPOST Repository | Thu Mar 16 00:00:00 GMT 2023

REPOSITORIES: jPOST

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			Action	DRS
	20191129_AR_inputphospho_F.msf	Msf
	20191129_AR_phospho_F.msf	Msf
	20191129_AR_phospho_F.pdResult	Other
	20191129_AR_phospho_F1.raw	Raw
	20191129_AR_phospho_F2.raw	Raw

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Publications

WNTinib is a multi-kinase inhibitor with specificity against β-catenin mutant hepatocellular carcinoma.

Rialdi Alex A Duffy Mary M Scopton Alex P AP Fonseca Frank F Zhao Julia Nanyi JN Schwarz Megan M Molina-Sanchez Pedro P Mzoughi Slim S Arceci Elisa E Abril-Fornaguera Jordi J Meadows Austin A Ruiz de Galarreta Marina M Torre Denis D Reyes Kyna K Lim Yan Ting YT Rosemann Felix F Khan Zaigham M ZM Mohammed Kevin K Wang Xuedi X Yu Xufen X Lakshmanan Manikandan M Rajarethinam Ravisankar R Tan Soo Yong SY Jin Jian J Villanueva Augusto A Michailidis Eleftherios E De Jong Ype P YP Rice Charles M CM Marazzi Ivan I Hasson Dan D Llovet Josep M JM Sobota Radoslaw M RM Lujambio Amaia A Guccione Ernesto E Dar Arvin C AC

Nature cancer 20230803 8

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. β-Catenin (CTNNB1)-mutated HCC represents 30% of cases of the disease with no precision therapeutics available. Using chemical libraries derived from clinical multi-kinase inhibitor (KI) scaffolds, we screened HCC organoids to identify WNTinib, a KI with exquisite selectivity in CTNNB1-mutated human and murine models, including patient samples. Multiomic and target engagement analyses, combined with rescue expe ...[more]

PMID: 37537299

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