Characterization of the Pharmacokinetic Properties and In Vivo Efficacy of a Candidate Bone Marrow Niche Altering Compound
| Autor: | Boylan, David |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Druh dokumentu: | Diplomová práce |
| Popis: | Acute myeloid leukemia (AML) is an aggressive cancer of the blood and bone marrow (BM) which affects the myeloid lineage of the hematopoietic hierarchy and causes the accumulation of immature and non-functional myeloid progenitor cells. While chemotherapy is generally effective at achieving remission in AML patients, long-term survival remains low due to the high rates of treatment related mortality among elderly patients as well as the high incidence of relapse, necessitating the development of novel therapeutics. Compounds which can influence mesenchymal stem cell (MSC) differentiation in the BM niche are of particular interest due to the role these cells play in HSC regulation as well as their disruption during AML disease progression. Our lab has utilized a phenotypic screen to discover compounds which could induce adipogenesis in BM-MSCs. Predicting which of these hit compounds are likely to be effective inducers of adipogenesis within the BM niche could streamline the drug discovery process by eliminating the need to examine the in vivo efficacy for compounds which are likely to be ineffective. Here, we aimed to evaluate if the in vivo efficacy of an MSC modulating compound could be predicted in vitro by assessing the compound’s bioavailability using a novel pharmacokinetic model and comparing the compound’s concentration in circulation to the minimum effective concentration observed in an in vitro phenotypic screen. Thesis Master of Science (MSc) |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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