Booth Id:
TMED052
Category:
Translational Medical Science
Year:
2023
Finalist Names:
Otos, Grace (School: North Carolina School of Science and Mathematics)
Abstract:
In-cell click-formed proteolysis targeting chimera molecules (CLIPTACs) were
developed to allow both the inhibition and ubiquitination (degradation) of mutated proteins
causing various diseases, including cancer. A CLIPTAC has two precursor molecule parts: the
protein binding section and the E3 binding section, that link through click chemistry after
delivery to the cell. No known CLIPTAC molecules have been developed for the treatment of
EGFR mutated cancers. Mutated EGFR is correlated with uncontrolled cancer growth and cell
division. The development of a CLIPTAC molecule for EGFR would prevent developed drug
resistance while treating these cancers. This project computationally identified a potential
CLIPTAC protein binding probe molecule for drug treatment of EGFR mutated cancer based
on the structure of Dacomitinib, and established EGFR inhibitor, using Schrodinger Maestro.
The identified molecule was then synthesized up through 3 of the 4 steps of its proposed
synthesis. Computational design and synthesis procedure indicate that the entire molecule can be
effectively synthesized and combined with an established E3 binding precursor molecule to form
a successful CLIPTAC.