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Pancreatic Neoplasms: HELP
Articles by Kenji Schorpp
Based on 1 article published since 2010
(Why 1 article?)

Between 2010 and 2020, Kenji Schorpp wrote the following article about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article Novel small molecules targeting ciliary transport of Smoothened and oncogenic Hedgehog pathway activation. 2016

Jung, Bomi / Messias, Ana C / Schorpp, Kenji / Geerlof, Arie / Schneider, Günter / Saur, Dieter / Hadian, Kamyar / Sattler, Michael / Wanker, Erich E / Hasenöder, Stefan / Lickert, Heiko. ·Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Germany. · Institute of Stem Cell Research, Helmholtz Zentrum München, Germany. · Institute of Structural Biology, Helmholtz Zentrum München, Germany. · Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemistry, Technische Universität München, 85747 Garching, Germany. · Assay Development and Screening Platform, Helmholtz Zentrum München, Germany. · Department of Internal Medicine II, Klinikum rechts der Isar, München, Germany. · Technische Universität München, München, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. · German Cancer Research Center (DKFZ), Heidelberg, Germany. · Neuroproteomics, Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany. · German Center for Diabetes Research (DZD), Germany. ·Sci Rep · Pubmed #26931153.

ABSTRACT: Trafficking of the G protein-coupled receptor (GPCR) Smoothened (Smo) to the primary cilium (PC) is a potential target to inhibit oncogenic Hh pathway activation in a large number of tumors. One drawback is the appearance of Smo mutations that resist drug treatment, which is a common reason for cancer treatment failure. Here, we undertook a high content screen with compounds in preclinical or clinical development and identified ten small molecules that prevent constitutive active mutant SmoM2 transport into PC for subsequent Hh pathway activation. Eight of the ten small molecules act through direct interference with the G protein-coupled receptor associated sorting protein 2 (Gprasp2)-SmoM2 ciliary targeting complex, whereas one antagonist of ionotropic receptors prevents intracellular trafficking of Smo to the PC. Together, these findings identify several compounds with the potential to treat drug-resistant SmoM2-driven cancer forms, but also reveal off-target effects of established drugs in the clinics.