Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 7 of 7 for “"Target deconvolution"”.
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Improved In Silico Methods for Target Deconvolution in Phenotypic Screens
Target-based screening projects for bioactive (orphan) compounds have been shown in many cases to be insufficiently predictive for in vivo efficacy, leading to attrition in clinical trials. Phenotypic screening has hence undergone a renaissance in both academia and in the pharmaceutical industry, …
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New approaches to antimalarial target deconvolution and measuring fitness effects of Plasmodium falciparum mutations implicated in drug resistance.
… are in development. However, in most cases, the targets and the mechanisms of action of these compounds are unknown. Understanding which compounds are targeting new pathways for which no resistance exists is critical to prioritising novel drug candidates. Understanding drug resistance in more …
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Chemical Tools for Exploring Metabolite Interactions with Nuclear Receptors and Beyond
… by these methods. New activity-based probes and targeted chemical reporters of specific protein families are thus needed to characterize their endogenous and exogenous ligands for fundamental biology and drug discovery. In this thesis, we describe two projects aimed at developing chemical probes …
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Computational analyses of small molecules activity from phenotypic screens
… on the one gene-one disease paradigm nor on target-based screening alone to discover new drugs. Phenotypic-based screening is regaining momentum to discover new compounds since those assays provide an environment closer to the physiological state of the disease and allow to better anticipate …
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Mechanism of Action Studies of Phenotypic Whole-cell Active Antimalarial Leads Through Target Identification
… represent one of the genomics tools for target deconvolution of hit and lead molecules. The mechanism of resistance of the pyrido[1,2- a]benzimidazoles was investigated through resistance selection. Whole-genome sequencing of the mutant clones generated from KP68 under drug pressure …
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Using Heterogeneous Information Sources for Understanding and Predicting Biological Effects of Compounds
… of new data modalities such as PROteolysis TArgeting Chimeras (PROTACs). In the first chapter, “Probabilistic Random Forest improves bioactivity predictions close to the classification threshold by taking into account experimental uncertainty”, a novel algorithm was evaluated and …
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Development of novel receptor tyrosine kinase inhibitors by a chemocentric approach
… inhibit a previously-validated specific target. This is referred to as target-based drug discovery. It was hoped that adopting this approach would usher in a new golden age of drug discovery. However, this has not been the case, with issues arising such as the target’s mechanism of action …