Supplementary Table S2 from Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

Thress, Kenneth; MacIntyre, Terry; Wang, Haiyun; Whitston, Dave; Liu, Zhong-Ying; Hoffmann, Ethan; Wang, Tao; Brown, Jeffrey L.; Webster, Kevin; Omer, Charles; Zage, Peter E.; Zeng, Lizhi; Zweidler-McKay, Patrick A.

doi:10.1158/1535-7163.22485869.v1

15357163mct090036-sup-mct-09-0036--suppl_table_2.pdf (44.66 kB)

Supplementary Table S2 from Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

journal contribution

posted on 2023-03-31, 23:30 authored by Kenneth Thress, Terry MacIntyre, Haiyun Wang, Dave Whitston, Zhong-Ying Liu, Ethan Hoffmann, Tao Wang, Jeffrey L. Brown, Kevin Webster, Charles Omer, Peter E. Zage, Lizhi Zeng, Patrick A. Zweidler-McKay

Supplementary Table S2 from Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

History

ARTICLE ABSTRACT

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. [Mol Cancer Ther 2009;8(7):1818–27]