Oncogenic mutations in the RAS family of genes (KRAS, HRAS, and NRAS) are present in approximately 30% of cancer. RAS plays a pivotal role in signal transduction pathways leading to tumor cell proliferation and survival. Our program has identified novel indene-based small molecules that exhibit potent and selective inhibition of activated RAS signaling regardless of isoform or mutation, or pan-RAS inhibition.
Abbreviations: EGFR=epidermal growth factor receptor, ERK=extracellular signal-regulated kinase, GRB2=Growth factor receptor-bound protein 2, MEK=mitogen activated protein kinase,
P=phosphorylated, PI3K = phosphatidylinositol 3-kinase, PIP2=phosphatidylinositol (4,5)-bisphosphate, PIP3=phosphatidylinositol (3,4,5)-trisphosphate, SOS=son of sevenless
Novel RAS Inhibitor, MCI-062, potently and selectively inhibits the growth of KRAS mutant pancreatic tumor cells by blocking GTP loading of RAS. Mattox et al. AACR Annual Meeting 2019. [Download Poster]
Targeting RAS and downstream signaling in high-grade serious ovarian carcinoma with novel RAS inhibitors. Mattox et al. AACR Annual Meeting 2019. [Download Poster]
A novel RAS Inhibitor, MCI-062, inhibits colon tumor growth in vivo and activates antitumor immunity. Keeton et al. AACR Annual Meeting 2019.