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Ref Type Journal Article
PMID (19509272)
Authors Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA
Title Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 8 7 2009 Jul 1818-27 Mol Cancer Ther
URL
Abstract Text Tropomyosin-related kinases (TrkA, TrkB, and TrkC) are receptor tyrosine kinases that, along with their ligands, the neurotrophins, are involved in neuronal cell growth, development, and survival. The Trk-neurotrophin pathway may also play a role in tumorigenesis through oncogenic fusions, mutations, and autocrine signaling, prompting the development of novel Trk inhibitors as agents for cancer therapy. This report describes the identification of AZ-23, a novel, potent, and selective Trk kinase inhibitor. In vitro studies with AZ-23 showed improved selectivity over previous compounds and inhibition of Trk kinase activity in cells at low nanomolar concentrations. AZ-23 showed in vivo TrkA kinase inhibition and efficacy in mice following oral administration in a TrkA-driven allograft model and significant tumor growth inhibition in a Trk-expressing xenograft model of neuroblastoma. AZ-23 represents a potent and selective Trk kinase inhibitor from a novel series with the potential for use as a treatment for cancer.

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Molecular Profile Treatment Approach
NTRK1 over exp Trk Receptor Inhibitor (Pan)
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AZ-23 AZ-23 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
AZ-23 Trk Receptor Inhibitor (Pan) 33 AZ-23 is a selective TRK inhibitor, which potentially inhibits growth of TRK-expressing tumors (PMID: 19509272, PMID: 29119387).
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