Drug Polypharmacy: From Rational Design of Multi-agonists for Type 2 Diabetes to Off-target Effects of Lysosomotropic Drugs
Date of Award
Doctor of Philosophy (PhD)
Doyle, Robert P.
Chemistry | Physical Sciences and Mathematics
This thesis explores the concept of drug polypharmacy, from peptide-based multi-target therapeutics to 'off-target' drug interactions. Work herein highlights the rational design and evaluation of multi-agonistic peptides towards the development of a novel therapeutic for type 2 diabetes and obesity devoid of nausea and emesis. Discussed is the rational design and in vitro screening of, particularly, GEP44 and GGP817, along with in vivo testing of GEP44 in rats and shrews. Additionally, the evaluation of off-target effects of lysosomotropic drugs on liposomal activator proteins is discussed. The target specificity of liposomal activator proteins saposin B and saposin D are evaluated, with focus on the interactions of the lysosomotropic drugs Fenretinide and Atovaquone, in particular.
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Milliken, Brandon, "Drug Polypharmacy: From Rational Design of Multi-agonists for Type 2 Diabetes to Off-target Effects of Lysosomotropic Drugs" (2021). Dissertations - ALL. 1371.