Glucose transporters (GLUTs) regulate glucose uptake and are often overexpressed in several human tumors. To identify new chemotypes targeting GLUT1, we built a pharmacophore model and searched against a NCI compound database. Sixteen hit molecules with good docking scores were screened for GLUT1 inhibition and antiproliferative activities. From these, we identified that compounds 2, 5, 6 and 13 inhibited the cell viability in a dose-dependent manner and that the IC50s of 2 and 6 are<10 µM concentration in the HCT116 colon cancer cell line. Lead compound 13 (NSC295720) was a GLUT1 inhibitor. Docking studies show that GLUT1 residues Phe291, Phe379, Glu380, Trp388, and Trp412 were important for inhibitor binding.

中文翻译：

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基于配体的GLUT抑制剂设计作为潜在的抗肿瘤药物。

葡萄糖转运蛋白（GLUT）调节葡萄糖的摄取，并且在几种人类肿瘤中通常过表达。为了识别针对GLUT1的新化学型，我们建立了一个药效团模型并针对NCI化合物数据库进行了搜索。筛选了16个具有良好对接得分的命中分子，以检测其对GLUT1的抑制作用和抗增殖活性。从这些结果中，我们确定了化合物2、5、6和13以剂量依赖性方式抑制细胞活力，并且2和6的IC50在HCT116结肠癌细胞系中的浓度<10 µM。铅化合物13（NSC295720）是GLUT1抑制剂。对接研究表明，GLUT1残基Phe291，Phe379，Glu380，Trp388和Trp412对抑制剂结合很重要。