ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors
Inhibition from the extracellular signal-controlled kinases ERK1 and ERK2 (ERK1/2) provides a promising therapeutic strategy in cancers harboring activated RAS/RAF/MEK/ERK signaling pathways. Here, we describe an orally bioavailable and selective ERK1/2 inhibitor, ASN007, presently in clinical development to treat cancer. In preclinical studies, ASN007 shows strong antiproliferative activity in tumors harboring mutations in BRAF and RAS (KRAS, NRAS, and HRAS). ASN007 demonstrates activity inside a BRAFV600E mutant melanoma tumor model that’s resistant against BRAF and MEK inhibitors. The PI3K inhibitor copanlisib improves the antiproliferative activity of ASN007 in vitro as well as in vivo because of dual inhibition of RAS/MAPK and PI3K survival pathways. Our data give a rationale for evaluating ASN007 in RAS/RAF-driven tumors in addition to a mechanistic grounds for mixing ASN007 with PI3K inhibitors.