ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors Journal Article


Authors: Portelinha, A.; Thompson, S.; Smith, R. A.; Da Silva Ferreira, M.; Asgari, Z.; Knezevic, A.; Seshan, V.; de Stanchina, E.; Gupta, S.; Denis, L.; Younes, A.; Reddy, S.
Article Title: ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors
Abstract: Inhibition of the extracellular signal-regulated kinases ERK1 and ERK2 (ERK1/2) offers 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, currently in clinical development for the treatment of cancer. In preclinical studies, ASN007 shows strong antiproliferative activity in tumors harboring mutations in BRAF and RAS (KRAS, NRAS, and HRAS). ASN007 demonstrates activity in a BRAFV600E mutant melanoma tumor model that is resistant to BRAF and MEK inhibitors. The PI3K inhibitor copanlisib enhances the antiproliferative activity of ASN007 both in vitro and in vivo due to dual inhibition of RAS/MAPK and PI3K survival pathways. Our data provide a rationale for evaluating ASN007 in RAS/RAF-driven tumors as well as a mechanistic basis for combining ASN007 with PI3K inhibitors. © 2021
Keywords: biomarker; lymphoma; kras; pi3k; solid tumors; kinase inhibitor; erk; asn007; combinational therapy; raf/ras-driven cancers
Journal Title: Cell Reports Medicine
Volume: 2
Issue: 7
ISSN: 2666-3791
Publisher: Cell Press  
Date Published: 2021-07-20
Start Page: 100350
Language: English
DOI: 10.1016/j.xcrm.2021.100350
PROVIDER: scopus
PMCID: PMC8324497
PUBMED: 34337566
DOI/URL:
Notes: Article -- Export Date: 2 August 2021 -- Source: Scopus
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