title: Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part II.
abstract: TrkA/B/C receptor activation supports growth, survival, and differentiation of discrete neuronal populations during development, adult life, and ageing but also plays numerous roles in human disease onset and progression. Trk-specific inhibitors have therapeutic applications in cancer and pain and thus constitute a growing area of interest in oncology and neurology. There has been substantial growth in the number of structural classes of Trk inhibitors and the number of industrial entrants to the Trk inhibitor field over the past six years. Areas covered: In Part II of this two-part review, the discussion of recent patent literature covering Trk family inhibitors is continued from Part I and clinical research with Trk inhibitors is considered. Expert opinion: Trk has been molecularly targeted for over a decade resulting in the progressive evolution of structurally diversified Trk inhibitors arising from scaffold hopping and HTS efforts. Correspondingly, there have been a growing number of clinical investigations utilizing Trk inhibitors in recent years, with a particular focus on the treatment of NTRK-fusion positive cancers and chronic pain. The observed potential of Trk inhibitors to cause adverse CNS side effects however suggests the need for a more rigorous consideration of BBB permeation capabilities during drug development.
authors.affiliation: a Faculty of Medicine & Dentistry, Department of Oncology , University of Alberta , Edmonton , Canada.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Bailey
authors.affiliation: a Faculty of Medicine & Dentistry, Department of Oncology , University of Alberta , Edmonton , Canada.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
authors.affiliation: a Faculty of Medicine & Dentistry, Department of Oncology , University of Alberta , Edmonton , Canada.
authors.forename: Kristen
authors.initials: K
authors.lastname: Farrell
authors.affiliation: a Faculty of Medicine & Dentistry, Department of Oncology , University of Alberta , Edmonton , Canada.
authors.forename: Vadim
authors.initials: V
authors.lastname: Bernard-Gauthier
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D020917:Receptor, trkA / Q000037:antagonists & inhibitors*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors*; D020812:Receptor, trkC / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC
keywords: LOXO-101; NTRK1/2/3; TrkA; TrkB; TrkC; Tropomyosin receptor kinase; cancer treatment; chronic pain; entrectinib; oncology; pruritis; targeted therapy; tropomyosin receptor kinase inhibitor