Discovery of a Potent GLUT Inhibitor from a Library of Rapafucins by Using 3D Microarrays.

Journal Article (Journal Article)

Glucose transporters play an essential role in cancer cell proliferation and survival and have been pursued as promising cancer drug targets. Using microarrays of a library of new macrocycles known as rapafucins, which were inspired by the natural product rapamycin, we screened for new inhibitors of GLUT1. We identified multiple hits from the rapafucin 3D microarray and confirmed one hit as a bona fide GLUT1 ligand, which we named rapaglutin A (RgA). We demonstrate that RgA is a potent inhibitor of GLUT1 as well as GLUT3 and GLUT4, with an IC50 value of low nanomolar for GLUT1. RgA was found to inhibit glucose uptake, leading to a decrease in cellular ATP synthesis, activation of AMP-dependent kinase, inhibition of mTOR signaling, and induction of cell-cycle arrest and apoptosis in cancer cells. Moreover, RgA was capable of inhibiting tumor xenografts in vivo without obvious side effects. RgA could thus be a new chemical tool to study GLUT function and a promising lead for developing anticancer drugs.

Full Text

Duke Authors

Cited Authors

  • Guo, Z; Cheng, Z; Wang, J; Liu, W; Peng, H; Wang, Y; Rao, AVS; Li, R-J; Ying, X; Korangath, P; Liberti, MV; Li, Y; Xie, Y; Hong, SY; Schiene-Fischer, C; Fischer, G; Locasale, JW; Sukumar, S; Zhu, H; Liu, JO

Published Date

  • November 25, 2019

Published In

Volume / Issue

  • 58 / 48

Start / End Page

  • 17158 - 17162

PubMed ID

  • 31591797

Pubmed Central ID

  • PMC6861656

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

Digital Object Identifier (DOI)

  • 10.1002/anie.201905578


  • eng

Conference Location

  • Germany