Identification of new GLUT2-selective inhibitors through in silico ligand screening and validation in eukaryotic expression systems.
Computer Simulation
Diabetes Mellitus
/ drug therapy
Drug Discovery
Fanconi Syndrome
/ drug therapy
Glucose
/ genetics
Glucose Transporter Type 2
/ antagonists & inhibitors
Glucose Transporter Type 5
/ antagonists & inhibitors
Humans
Ligands
Neoplasms
/ drug therapy
Protein Conformation
/ drug effects
Small Molecule Libraries
/ chemistry
User-Computer Interface
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 07 2021
02 07 2021
Historique:
received:
03
05
2021
accepted:
14
06
2021
entrez:
3
7
2021
pubmed:
4
7
2021
medline:
6
11
2021
Statut:
epublish
Résumé
Glucose is an essential energy source for cells. In humans, its passive diffusion through the cell membrane is facilitated by members of the glucose transporter family (GLUT, SLC2 gene family). GLUT2 transports both glucose and fructose with low affinity and plays a critical role in glucose sensing mechanisms. Alterations in the function or expression of GLUT2 are involved in the Fanconi-Bickel syndrome, diabetes, and cancer. Distinguishing GLUT2 transport in tissues where other GLUTs coexist is challenging due to the low affinity of GLUT2 for glucose and fructose and the scarcity of GLUT-specific modulators. By combining in silico ligand screening of an inward-facing conformation model of GLUT2 and glucose uptake assays in a hexose transporter-deficient yeast strain, in which the GLUT1-5 can be expressed individually, we identified eleven new GLUT2 inhibitors (IC
Identifiants
pubmed: 34215797
doi: 10.1038/s41598-021-93063-5
pii: 10.1038/s41598-021-93063-5
pmc: PMC8253845
doi:
Substances chimiques
Glucose Transporter Type 2
0
Glucose Transporter Type 5
0
Ligands
0
SLC2A2 protein, human
0
Small Molecule Libraries
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
13751Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM123103
Pays : United States
Références
Front Mol Biosci. 2021 Feb 18;7:598419
pubmed: 33681287
Diabetologia. 2015 Feb;58(2):221-32
pubmed: 25421524
PLoS One. 2016 Nov 16;11(11):e0165585
pubmed: 27851758
Sci Rep. 2015 Aug 26;5:12804
pubmed: 26306809
Nature. 2014 Jun 5;510(7503):121-5
pubmed: 24847886
Cell Physiol Biochem. 2003;13(3):123-34
pubmed: 12876383
Am J Physiol Regul Integr Comp Physiol. 2020 Jan 1;318(1):R38-R48
pubmed: 31596114
Diabetologia. 2018 Oct;61(10):2087-2097
pubmed: 30132032
Diabetes. 2011 Oct;60(10):2598-607
pubmed: 21852673
Pflugers Arch. 2020 Sep;472(9):1155-1175
pubmed: 32591905
Pflugers Arch. 2020 Sep;472(9):1299-1343
pubmed: 32789766
Int J Biol Sci. 2015 Mar 19;11(5):508-24
pubmed: 25892959
J Agric Food Chem. 2016 Sep 14;64(36):6826-37
pubmed: 27538679
Int J Mol Sci. 2020 Aug 31;21(17):
pubmed: 32877990
Mol Membr Biol. 2001 Oct-Dec;18(4):247-56
pubmed: 11780753
J Virol. 2012 Dec;86(23):12903-11
pubmed: 22993150
Oncotarget. 2017 Aug 14;8(40):68381-68392
pubmed: 28978124
Int J Cancer. 2009 May 1;124(9):2210-9
pubmed: 19123483
Am J Physiol Gastrointest Liver Physiol. 2015 Nov 1;309(9):G779-90
pubmed: 26316589
Metabolism. 2016 Feb;65(2):124-39
pubmed: 26773935
FEBS Lett. 2002 Jul 31;524(1-3):199-203
pubmed: 12135767
Front Chem. 2018 May 25;6:183
pubmed: 29888221
J Physiol. 2001 Mar 15;531(Pt 3):585-95
pubmed: 11251042
Biochem Biophys Res Commun. 2013 May 3;434(2):346-51
pubmed: 23548572
Mol Metab. 2016 Nov 04;6(1):61-72
pubmed: 28123938
FASEB J. 2007 Feb;21(2):366-77
pubmed: 17172639
Sci Rep. 2017 Jul 24;7(1):6197
pubmed: 28740135
J Chem Inf Model. 2011 Mar 28;51(3):578-96
pubmed: 21323318
Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17862-7
pubmed: 24127585
Cell. 2005 Dec 29;123(7):1307-21
pubmed: 16377570
Biochemistry. 1991 Apr 23;30(16):3907-15
pubmed: 2018762
Diabetes. 2005 Oct;54(10):3056-62
pubmed: 16186415
Open Biol. 2014 Jul;4(7):
pubmed: 25056286
J Cell Physiol. 2006 Jun;207(3):614-27
pubmed: 16523487
Mol Aspects Med. 2013 Apr-Jun;34(2-3):121-38
pubmed: 23506862
Angew Chem Int Ed Engl. 2019 Nov 18;58(47):17016-17025
pubmed: 31469221
Physiol Rev. 2010 Jan;90(1):23-46
pubmed: 20086073
Nature. 2012 Oct 18;490(7420):361-6
pubmed: 23075985
Cell Chem Biol. 2019 Sep 19;26(9):1214-1228.e25
pubmed: 31303578
Cancer Metab. 2021 Mar 26;9(1):14
pubmed: 33771231
J Physiol. 1973 May;231(1):143-65
pubmed: 4715343
European J Org Chem. 2020 May 3;2020(16):2321-2329
pubmed: 32421048
Nature. 2015 Oct 15;526(7573):397-401
pubmed: 26416735
J Biol Chem. 2002 May 3;277(18):15252-60
pubmed: 11834736
J Cell Sci. 2000 Mar;113 ( Pt 5):841-7
pubmed: 10671373
Stem Cells Transl Med. 2013 Dec;2(12):929-34
pubmed: 24167319
Biochem J. 1993 Mar 15;290 ( Pt 3):701-6
pubmed: 8457197
Nat Rev Mol Cell Biol. 2016 Feb;17(2):123-32
pubmed: 26758938
J Biol Chem. 2017 Dec 22;292(51):21035-21046
pubmed: 29066623
Glycobiology. 2020 Aug 20;30(9):722-734
pubmed: 32149357
Hum Genet. 2002 Jan;110(1):21-9
pubmed: 11810292
Sci Rep. 2016 Apr 14;6:24240
pubmed: 27074918
Physiol Genomics. 2008 May 13;33(3):355-60
pubmed: 18349384
Biochim Biophys Acta. 1997 Feb 21;1324(1):111-9
pubmed: 9059504
Am J Physiol Endocrinol Metab. 2010 May;298(5):E1078-87
pubmed: 20179244
Mol Nutr Food Res. 2012 Mar;56(3):435-45
pubmed: 22173993
Nature. 2015 Oct 15;526(7573):391-6
pubmed: 26176916
FEBS J. 2018 Aug;285(16):2926-2943
pubmed: 29893496
Mol Membr Biol. 2001 Oct-Dec;18(4):265-73
pubmed: 11780755