作为mTOR信号通路抗癌抑制剂的苯并呋喃衍生物
Benzofuran derivatives as anticancer inhibitors of mTOR signaling.
作者信息
Salomé Christophe, Ribeiro Nigel, Chavagnan Thierry, Thuaud Frédéric, Serova Maria, de Gramont Armand, Faivre Sandrine, Raymond Eric, Désaubry Laurent
机构信息
Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France.
AAREC Filia Research, 1 Place Paul Verlaine, 92100 Boulogne-Billancourt, France.
出版信息
Eur J Med Chem. 2014 Jun 23;81:181-91. doi: 10.1016/j.ejmech.2014.05.014. Epub 2014 May 5.
A series of 32 derivatives and isosteres of the mTOR inhibitor 2 were synthesized and compared for their cytotoxicity in radioresistant SQ20B cancer cell line. Several of these compounds, in particular 30b, were significantly more cytotoxic than 2. Importantly, 30b was shown to block both mTORC1 and Akt signaling, suggesting insensitivity to the resistance associated to Akt overactivation observed with rapamycin derivatives currently used in clinic.
合成了一系列32种mTOR抑制剂2的衍生物和生物电子等排体，并比较了它们在耐辐射的SQ20B癌细胞系中的细胞毒性。其中几种化合物，特别是30b，其细胞毒性明显高于2。重要的是，30b被证明能阻断mTORC1和Akt信号传导，这表明它对目前临床上使用的雷帕霉素衍生物所观察到的与Akt过度激活相关的耐药性不敏感。
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