2. Academic Validation
  3. ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors

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

  • Cell Rep Med. 2021 Jul 21;2(7):100350. doi: 10.1016/j.xcrm.2021.100350.
Ana Portelinha 1,  Scott Thompson 2,  Roger A Smith 2,  Mariana Da Silva Ferreira 1,  Zahra Asgari 1,  Andrea Knezevic 3,  Venkatraman Seshan 3,  Elisa de Stanchina 4,  Sandeep Gupta 2,  Louis Denis 2,  Anas Younes 1 5,  Sanjeeva Reddy 2
Affiliations

Affiliations

  • 1 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 2 Asana BioSciences, Lawrenceville, NJ, USA.
  • 3 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 4 Antitumor Assessment Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 5 Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
PMID: 34337566 DOI: 10.1016/j.xcrm.2021.100350
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.

Keywords

ASN007; ERK; KRAS; PI3K; RAF/RAS-driven cancers; biomarker; combinational therapy; kinase inhibitor; lymphoma; solid tumors.

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