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RET kinase inhibitors: a review of recent patents (2012-2015).

INTRODUCTION: 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.

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