title: RET kinase inhibitors: a review of recent patents (2012-2015).
abstract: Tyrosine kinases are involved in the control of several biological processes and have been recognized as hot spots of oncogenic transformation, thus representing a major therapeutic target. Dysregulated activation of RET kinase, either through point mutations or gene fusions, is accountable for a significant fraction of thyroid carcinomas, as well as a minor population of lung cancers. Two drugs are currently available for the treatment of medullary thyroid carcinoma and two additional compounds have been approved for differentiated thyroid carcinoma. Several other molecules are under preclinical and clinical evaluation. Areas covered: This review covers the most recent patent literature (2012-2015) describing compounds with activity against the RET kinase, trying to catch a view of the next generation of potential anti-RET drugs. Expert opinion: RET has been a focus of molecularly targeted efforts for over a decade. However, none of the drugs currently on the clinical stage were specifically developed to hit RET, which was rather an off-target. Besides, only two of four drugs have activity on metastatic medullary carcinoma. Therefore, there is still a need of additional, more potent and more specific RET inhibitors, which will hopefully emerge from the new generation of compounds disclosed in most recent patents.
authors.affiliation: a School of Medicine and Surgery , University of Milano-Bicocca , Monza , Italy.|d Galkem srl , Monza , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Mologni
authors.affiliation: a School of Medicine and Surgery , University of Milano-Bicocca , Monza , Italy.|d Galkem srl , Monza , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
authors.affiliation: b Chimie Organique 2-Glycosciences , University of Lyon , Lyon , France.|d Galkem srl , Monza , Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Goekjian
authors.affiliation: c School of Pharmaceutical Sciences , University of Geneva , Geneva , Switzerland.|d Galkem srl , Monza , Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scapozza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000473:pathology; D015195:Drug Design; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret
keywords: RET; RET/PTC; cabozantinib; non-small cell lung cancer; precision medicine; thyroid cancer; vandetanib