We have two small molecule preclinical development programs targeting oncogenic pathways, focused on RAS and PDE10/ß-catenin, respectively.
Pan-RAS Program: 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.
PDE10/ß-catenin Program: Genetic alterations in com that make up the Wnt signaling pathway, which includes APC (adenomatous polyposis coli) and β-catenin, are prevalent in a number of cancer types, occurring in upwards of 80% of colorectal cancers. Our program has identified small molecules that selectively and potently inhibit PDE10 and suppress Wnt/β-catenin signaling in preclinical models. PDE10 inhibition has been shown to down regulate β-catenin expression and inhibits polyp and tumor growth. It has potential for application in the treatment of cancer as well as spontaneous and familial polyposis syndromes.