- Discovery of wtRET and V804MRET Inhibitors: From Hit to Lead
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Oncogenic activation of RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma, and non-small-cell lung cancer. Currently approved RET inhibitors were not originally designed to be RET inhibitors, and their potency against RET kinase has not been optimized. Hence, novel compounds able to inhibit both wild-type RET (wtRET) and its mutants (e.g., V804MRET) are needed. Herein we present the development and the preliminary evaluation of a new sub-micromolar wtRET/V804MRET inhibitor, N-(2-fluoro-5-trifluoromethylphenyl)-N′-{4′-[(2′′-benzamido)pyridin-4′′-ylamino]phenyl}urea (69), endowed with a 4-anilinopyridine structure, starting from our previously identified 4-anilinopyrimidine hit compound. Profiling against a panel of kinases indicated 69 as a multi cKIT/wtRET/V804MRET inhibitor.
- Mologni, Luca,Dalla Via, Martina,Chilin, Adriana,Palumbo, Manlio,Marzaro, Giovanni
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p. 1390 - 1398
(2017/09/01)
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- PYRIMIDINES USEFUL AS MODULATORS OF VOLTAGE-GATED ION CHANNELS
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The present invention relates to compounds useful as inhibitors of voltage-gated ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
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Page 129-130
(2010/02/10)
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