Biomedical Engineering ETDs
Publication Date
Spring 5-15-2020
Abstract
Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound under investigation, PR-619, was shown to be a pan-GTPase inhibitor that competitively inhibits guanine nucleotide binding in a panel of sixteen members of the Ras superfamily of small GTPases. Additionally, PR-619 was demonstrated to inhibit GTPase-effector interaction and to produce effects in cellular studies.
Language
English
Keywords
GTPase, inhibitor, competitive, high throughput screening, drug discovery, multiplex
Document Type
Thesis
Degree Name
Biomedical Engineering
Level of Degree
Masters
Department Name
Biomedical Engineering
First Committee Member (Chair)
Dr. Larry A. Sklar
Second Committee Member
Dr. Steven Graves
Third Committee Member
Dr. Andrew Shreve
Fourth Committee Member
Dr. Angela Wandinger-Ness
Recommended Citation
Akhadov, Leyla. "Screening and Characterization of a Pan-GTPase Inhibitor." (2020). https://digitalrepository.unm.edu/bme_etds/30
Included in
Chemicals and Drugs Commons, Other Biomedical Engineering and Bioengineering Commons, Other Medicine and Health Sciences Commons
