SHP2, a protein-tyrosine
phosphatase (PTP), is a key signaling regulator in multiple cell signaling
processes including the Ras/MAPK pathway. This has led to SHP2 being identified
as a therapeutic target in multiple types of cancers and autoimmune disorders.
However, the role that the C-terminal residues play when they interact with
other SHP2 domains remains unknown. This study presents data to illustrate that
the C-terminal residues interact intramolecularly with other domains to inhibit
PTP activity. Additionally, the identification of a specific and potent SHP2
inhibitor has proven difficult because of the high homology and positive nature
of the PTP active site. This study presents the data from a high throughput
fragment screen identifying several promising HIT compounds that may be further
developed into potent and selective SHP2 inhibitors. Furthermore, data
supporting the development of a selective SHP2 covalent inhibitor from a
nonselective core molecule is presented.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/8300651 |
| Date | 12 October 2021 |
| Creators | Erica Anne Baker (6860789) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/KINETIC_STUDY_OF_ONCOGENIC_PHOSPHATASE_SHP2_AND_ITS_CORRESPONDING_INHIBITORS/8300651 |
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