Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: doi:10.22028/D291-31437
Titel: Development of novel drug-like molecules for targeted therapy
VerfasserIn: Siebenbürger, Lorenz Albrecht
Sprache: Englisch
Erscheinungsjahr: 2019
DDC-Sachgruppe: 540 Chemie
570 Biowissenschaften, Biologie
Dokumenttyp: Dissertation
Abstract: Implementation of novel techniques such as high-resolution mass-spectrometry, next generation sequencing or computer simulations have altered our understanding of diseases. Therapy forms emerge that turn away from the one-fits-all paradigm towards highly specialized targeted therapies. These novel medications increase efficacy in smaller groups of patients, and reduce side effects observed with outdated broad-spectrum drugs. Oncology research has been a pioneer in this field, but the concept can also be applied to other pharmacological areas such as endocrinology. The first part of this thesis deals with the development of novel anti-angiogenic drugs for targeted-cancer therapy. Novel matrix metalloprotease inhibitors were synthesized, targeting a structurally less conserved part of enzyme class. High activity and selectivity could be achieved in different cancer cell lines, depending on the molecular structure of the inhibitors. Part two deals with the development of 17β-HSD2 inhibitors for targeted-endocrine therapy of decreased bone fracture healing and osteoporosis. First, a class of inhibitors was optimized in activity, selectivity and metabolic stability to be successfully tested in an in vivo proof-of-principle mouse fracture model, leading to highly increased stability of the fractures. In a second step, this class was simplified and further optimized for osteoporosis therapy, showing increased properties after oral administration in a mouse pharmacokinetic study.
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-314377
hdl:20.500.11880/29450
http://dx.doi.org/10.22028/D291-31437
Erstgutachter: Hartmann, Rolf. W.
Tag der mündlichen Prüfung: 28-Feb-2020
Datum des Eintrags: 22-Jul-2020
Drittmittel / Förderung: BMBF KNOCHSDIN
Fördernummer: 031A467
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Pharmazie
Professur: NT - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Dateien zu diesem Datensatz:
Datei Beschreibung GrößeFormat 
20200707_Doktorarbeit_LS_final_Pub.pdfDissertation24,48 MBAdobe PDFÖffnen/Anzeigen


Alle Ressourcen in diesem Repository sind urheberrechtlich geschützt.