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Discovery of small molecules blocking oncogenic K-Ras activity

Kovar, Sarah E.
http://orcid.org/0000-0002-5268-6038
http://rave.ohiolink.edu/etdc/view?acc_num=wright1533299266181661

Abstract Details

2018, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
Ras proteins were the first human oncogenes discovered. Although Ras has been found to be the most frequently mutated oncogene, there are currently no anti-Ras-specific drugs available in the clinic. Ras is responsible for initiating cellular pathways that include proliferation, survival, and apoptosis. There are three ubiquitously expressed Ras isoforms in mammalian cells: H-, N-, and K-Ras. Interaction with the plasma membrane is required for Ras biological activity. When Ras interaction with the plasma membrane is blocked, Ras activity is inhibited. Two compounds (from Dr. Ketcha, WSU Chemistry Department) were tested and shown to dissociate K-Ras, but not H-Ras from the plasma membrane. The molecular mechanism was found to be through phosphorylation of K-Ras Ser181. Furthermore, these compounds block signal output of K-Ras, but not H-Ras, and inhibit the growth of K-Ras-driven non-small cell lung cancer cells. Further characterization of these compounds could lead to the development of anti-K-Ras drugs.
Kwang-Jin Cho, Ph.D. (Advisor)
Daniel Ketcha, Ph.D. (Committee Member)
Weiwen Long, Ph.D. (Committee Member)
Michael Markey, Ph.D. (Committee Member)
Hongmei Ren, Ph.D. (Committee Member)
84 p.
Biochemistry; Molecular Biology
K-Ras; oncogenic Ras; K-Ras Ser181; phosphorylation; signal transduction; non-small cell lung cancer cells

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Citations

  • Kovar, S. E. (2018). Discovery of small molecules blocking oncogenic K-Ras activity [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1533299266181661

    APA Style (7th edition)

  • Kovar, Sarah. Discovery of small molecules blocking oncogenic K-Ras activity. 2018. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1533299266181661.

    MLA Style (8th edition)

  • Kovar, Sarah. "Discovery of small molecules blocking oncogenic K-Ras activity." Master's thesis, Wright State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1533299266181661

    Chicago Manual of Style (17th edition)

wright1533299266181661
130
© 2018, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.