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Open Access Small Molecules Targeting the Hedgehog Pathway: From Phenotype to Mechanistic Understanding

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This article is Open Access under the terms of the Creative Commons CC BY-NC licence.

Since the beginning of 2019, the Hoogendoorn lab is active at the University of Geneva. We are a Chemical Biology lab and our research focuses on the Hedgehog (Hh) signalling pathway and the primary cilium, a small cellular organelle which corrects structure and function, is required to conduct the Hh signal. Ciliary Hh signalling plays an important role in embryonic development, and its dysregulation consequently results in developmental disorders as well as a variety of cancers. We use an interdisciplinary approach, ranging from organic chemistry to cell biology and genetics, to develop chemical tools to study and perturb ciliary signalling. In this account, I will highlight existing small molecules that target the Hh pathway, our efforts to discover new compounds, and the methodologies that we employ for target deconvolution and mechanism of action studies.
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Keywords: CHEMICAL BIOLOGY; HEDGEHOG SIGNALLING; PHENOTYPIC SCREENS; SMALL-MOLECULE PROBES; TARGET IDENTIFICATION

Document Type: Research Article

Affiliations: University of Geneva, Department of Organic Chemistry, NCCR Chemical Biology, Quai Ernest-Ansermet 30, CH-1211 Gèneve, Switzerland;, Email: [email protected]

Publication date: September 1, 2020

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  • International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions

    CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.

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