Date of Award
2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
Committee Chair
Ifedayo Victor Ogungbe
Committee Member
Pamela Twigg
Committee Member
Sharifa Love-Rutledge
Research Advisor
Ifedayo Victor Ogungbe
Subject(s)
Antibody-drug conjugates--Synthesis, Liver--Cancer--Treatment, Protease inhibitors
Abstract
The treatment of hepatocellular carcinoma (HCC) experiences several limitations due to the advanced stage of the disease upon diagnosis. Thus, the focus of HCC treatment in recent years has been on the development and design of chemotherapeutic agents capable of targeting and eliminating HCC that has metastasized from the liver tissue. Antibody-drug conjugates (ADCs) are a novel technology whose development is being pursued due to decreased displays of off-target toxicity that are experienced following current systemic treatment options. This work seeks to develop an ADC that implements the cytotoxic effects of NN9-OH, a vinyl-sulfone covalent inhibitor of lysosomal cathepsins as an option to treat HCC. The synthesis of NN9-OH has been optimized and the compound has been characterized in both structure and inhibitory capabilities. However, the next phase of the ADC synthesis, the conjugation of NN9-OH to the linker, MC-Val-Ala-OH, is still in progress.
Recommended Citation
Sizemore, Drake Alexander, "Studies toward the synthesis of an antibody–drug conjugate (ADC) as an approach to treat hepatocellular carcinoma by inhibiting cathepsins" (2025). Theses. 763.
https://louis.uah.edu/uah-theses/763