The MEK5/ERK5 pathway regulates various cellular processes, including proliferation, differentiation, apoptosis, and migration. The MEK5/ERK5 pathway is upregulated in multiple types of cancer. In breast cancer, upregulation of the MEK5 pathway is linked to the development of chemotherapeutic drug resistance, poorer relapse-free survival, epithelial-to-mesenchymal transition (EMT), and metastasis. The MEK and PI3K/AKT pathways are known to be interconnected by several control mechanisms. The inhibition of one pathway leads to compensatory activation of another pathway potentiating cell survival. Simultaneous inhibition of both MEK5 and PI3K/AKT pathways synergistically reduces cell viability and migration in various breast cancer and glioblastoma cell lines. Our initial cellular testing in MDA-MB-231 cells identified quinazoline derivatives as dual MEK5 and PI3K inhibitors. Further optimization, computational modeling, chemical synthesis, and <i>in-vitro</i> testing will be presented.

Design, synthesis, and biological evaluation of dual inhibitors of mitogen-activated protein kinase 5 (MEK5) and phosphatidylinositol 3-kinase (PI3K) pathway

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.