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Ref Type Journal Article
PMID (34337566)
Authors Portelinha A, Thompson S, Smith RA, Da Silva Ferreira M, Asgari Z, Knezevic A, Seshan V, de Stanchina E, Gupta S, Denis L, Younes A, Reddy S
Title ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors.
Journal Cell reports. Medicine
Vol 2
Issue 7
Date 2021 Jul 20
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ERAS-007 ERAS-007 8 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
ERAS-007 ASN007|ASN-007|ASN 007|ERAS007|ERAS 007 ERK Inhibitor (pan) 17 ERAS-007 (ASN007) is a small molecule that inhibits ERK1/2, which may result in decreased tumor cell proliferation and reduced tumor growth (PMID: 34337566).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E diffuse large B-cell lymphoma sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of diffuse large B-cell lymphoma cells harboring BRAF V600E in culture (PMID: 34337566). 34337566
NRAS Q61R melanoma sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a melanoma cell line harboring NRAS Q61R in culture (PMID: 34337566). 34337566
NRAS G13D mantle cell lymphoma sensitive Copanlisib + ERAS-007 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of ERAS-007 (ASN007) and Aliqopa (copanlisib) inhibited tumor growth in a cell line xenograft model of mantle cell lymphoma harboring NRAS G13D, and demonstrated improved efficacy over either agent alone (PMID: 34337566). 34337566
BRAF V600E melanoma sensitive ERAS-007 Preclinical - Pdx & cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation and Erk signaling in a melanoma cell line harboring BRAF V600E in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models, including a Zelboraf (vemurafenib)-resistant PDX model (PMID: 34337566). 34337566
NRAS G13D mantle cell lymphoma sensitive ERAS-007 Preclinical - Cell line xenograft Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a mantle cell lymphoma cell line harboring NRAS G13D in culture and inhibited tumor growth in xenograft models (PMID: 34337566). 34337566
BRAF V600E colorectal cancer sensitive ERAS-007 Preclinical - Pdx & cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited cell proliferation and Erk signaling in colorectal cancer cell lines harboring BRAF V600E in culture, and induced tumor regression in two patient-derived xenograft (PDX) models (PMID: 34337566). 34337566
NRAS Q61L liver cancer sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a liver cancer cell line harboring NRAS Q61L in culture (PMID: 34337566). 34337566
NRAS Q61K neuroblastoma sensitive ERAS-007 Preclinical - Cell line xenograft Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited tumor growth in a neuroblastoma cell line xenograft model harboring NRAS Q61K (PMID: 34337566). 34337566
HRAS G12V urinary bladder cancer sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34337566). 34337566