Structure-Activity Relationship Study of Precision Drug to Target Stromal Antigen 2 Mutant Ewing Sarcoma

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dc.contributor.advisorGilbertson, Scott R.
dc.contributor.committeeMemberMay, Jeremy A.
dc.contributor.committeeMemberCuny, Gregory D.
dc.contributor.committeeMemberChen, Tai-Yen
dc.contributor.committeeMemberPati, Debananda
dc.contributor.committeeMemberDaugulis, Olafs
dc.creatorLin, Keng-fu 1987-
dc.creator.orcid0000-0001-6315-0477
dc.date.accessioned2019-12-17T03:32:06Z
dc.date.createdDecember 2019
dc.date.issued2019-12
dc.date.submittedDecember 2019
dc.date.updated2019-12-17T03:32:07Z
dc.description.abstractStagX1 was identified from a high throughput screen in 2017 to inhibit the growth of Ewing sarcoma cells by the laboratory of Dr. Debananda Pati at the Baylor College of Medicine. This drug candidate manifests excellent selectivity between stromal antigen 2 (STAG2) gene wild type and mutant cancer cells in the preliminary studies. Three synthetic routes have been proposed and investigated functional group modifications. Additional structure and activity studies have been exerted on StagX analogs as well and 25 StagX series compounds were synthesized and tested. StagX 1.4 and 1.12 shown below provide better pharmacokinetics as compared to the lead compound, StagX1. Two parts of StagX’s structure were confirmed to be strongly correlated to its selectivity. The heptyl group in StagX2.6 loses the selectivity between STAG2 mutant cancer cells and wild type cells. Furthermore, we found that the modification of benzylamine derivatives will fully eliminate the selectivity. These two modifications significantly influence the selectivity of targeting cells.
dc.description.departmentChemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657/5554
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectEWING SARCOMA
dc.subjectSTRUCTURE-ACTIVITY RELATIONSHIP STUDY
dc.titleStructure-Activity Relationship Study of Precision Drug to Target Stromal Antigen 2 Mutant Ewing Sarcoma
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2021-12-01
local.embargo.terms2021-12-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentChemistry, Department of
thesis.degree.disciplineChemistry
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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