Discovery of a Potent GLUT Inhibitor from a Library of Rapafucins by Using 3D Microarrays.
A549 Cells
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Drug Screening Assays, Antitumor
Glucose Transport Proteins, Facilitative
/ antagonists & inhibitors
Humans
MCF-7 Cells
Macrolides
/ chemistry
Molecular Structure
Phosphotransferases (Phosphate Group Acceptor)
/ metabolism
Protein Array Analysis
Signal Transduction
Sirolimus
/ chemistry
Small Molecule Libraries
/ chemistry
Structure-Activity Relationship
TOR Serine-Threonine Kinases
/ metabolism
Tacrolimus
/ chemistry
Tacrolimus Binding Proteins
GLUT1
antitumor compounds
drug discovery
high-throughput screening
inhibitors
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
25 11 2019
25 11 2019
Historique:
received:
05
05
2019
revised:
03
09
2019
pubmed:
9
10
2019
medline:
22
10
2020
entrez:
9
10
2019
Statut:
ppublish
Résumé
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 IC
Identifiants
pubmed: 31591797
doi: 10.1002/anie.201905578
pmc: PMC6861656
mid: NIHMS1054444
doi:
Substances chimiques
Antineoplastic Agents
0
Glucose Transport Proteins, Facilitative
0
Macrolides
0
Small Molecule Libraries
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
AMP-dependent kinase (ATP-forming)
EC 2.7.4.-
Phosphotransferases (Phosphate Group Acceptor)
EC 2.7.4.-
Tacrolimus Binding Proteins
EC 5.2.1.-
Sirolimus
W36ZG6FT64
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17158-17162Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : DP1 CA174428
Pays : United States
Organisme : Flight Attendant Medical Research Institute
Pays : International
Organisme : Damon Runyon Cancer Research Fund
Pays : International
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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