Tadalafil Rescues the p.M325T Mutant of Best1 Chloride Channel.
4PBA
COPII
FDA-approved
IRDs
bestrophin
tadalafil
virtual docking
whole-cell patch-clamp
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
08 Apr 2023
08 Apr 2023
Historique:
received:
27
02
2023
revised:
24
03
2023
accepted:
31
03
2023
medline:
1
5
2023
pubmed:
28
4
2023
entrez:
28
4
2023
Statut:
epublish
Résumé
Bestrophin 1 (Best1) is a chloride channel that localises to the plasma membrane of retinal pigment epithelium (RPE) cells. Mutations in the BEST1 gene are associated with a group of untreatable inherited retinal dystrophies (IRDs) called bestrophinopathies, caused by protein instability and loss-of-function of the Best1 protein. 4PBA and 2-NOAA have been shown to rescue the function, expression, and localisation of Best1 mutants; however, it is of interest to find more potent analogues as the concentration of the drugs required is too high (2.5 mM) to be given therapeutically. A virtual docking model of the COPII Sec24a site, where 4PBA has been shown to bind, was generated and a library of 1416 FDA-approved compounds was screened at the site. The top binding compounds were tested in vitro in whole-cell patch-clamp experiments of HEK293T cells expressing mutant Best1. The application of 25 μM tadalafil resulted in full rescue of Cl
Identifiants
pubmed: 37110551
pii: molecules28083317
doi: 10.3390/molecules28083317
pmc: PMC10142963
pii:
doi:
Substances chimiques
Bestrophins
0
Chloride Channels
0
Tadalafil
742SXX0ICT
BEST1 protein, human
0
SEC24A protein, human
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Sight Research UK
ID : RES 010
Références
J Cheminform. 2019 Jun 7;11(1):40
pubmed: 31175455
Elife. 2017 Jun 08;6:
pubmed: 28594326
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):4008-13
pubmed: 11904445
J Neurochem. 2005 Jun;93(5):1087-98
pubmed: 15934930
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12758-63
pubmed: 11050159
J Comput Chem. 2009 Dec;30(16):2785-91
pubmed: 19399780
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
pubmed: 11259830
Mol Pharmacol. 2004 Oct;66(4):899-908
pubmed: 15226415
J Ophthalmic Vis Res. 2021 Apr 29;16(2):248-259
pubmed: 34055262
J Cheminform. 2011 Oct 07;3:33
pubmed: 21982300
J Chem Inf Model. 2017 Dec 26;57(12):2911-2937
pubmed: 29243483
Prog Retin Eye Res. 2017 May;58:45-69
pubmed: 28153808
Dis Model Mech. 2016 Nov 1;9(11):1317-1328
pubmed: 27519691
J Med Chem. 2002 Jun 6;45(12):2615-23
pubmed: 12036371
Nucleic Acids Res. 2023 Jan 6;51(D1):D1373-D1380
pubmed: 36305812
Drugs. 2016 Aug;76(12):1191-201
pubmed: 27394157
Graefes Arch Clin Exp Ophthalmol. 2017 Jun;255(6):1057-1062
pubmed: 28285324
Int J Mol Sci. 2019 Sep 04;20(18):
pubmed: 31487867
P T. 2013 Jul;38(7):407-19
pubmed: 24049429
Front Pharmacol. 2012 Sep 18;3:167
pubmed: 23024633
Leukemia. 2006 Feb;20(2):212-7
pubmed: 16357841
J Clin Invest. 1997 Nov 15;100(10):2457-65
pubmed: 9366560
Prion. 2014 Mar-Apr;8(2):
pubmed: 24818993
Nat Rev Drug Discov. 2019 Jan;18(1):41-58
pubmed: 30310233
Nat Commun. 2022 Jul 4;13(1):3836
pubmed: 35789156
J Biochem Mol Toxicol. 2022 Aug;36(8):e23100
pubmed: 35608386
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
Phys Chem Chem Phys. 2016 May 14;18(18):12964-75
pubmed: 27108770
Int J Impot Res. 2004 Jun;16 Suppl 1:S28-33
pubmed: 15224133
Clin Cancer Res. 2009 Oct 1;15(19):6241-9
pubmed: 19789320
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Am Soc Nephrol. 2004 Jul;15(7):1731-8
pubmed: 15213260
Methods Mol Biol. 2013;998:91-107
pubmed: 23529423
Hum Genet. 2017 Jun;136(6):665-677
pubmed: 28349240
Invest Ophthalmol Vis Sci. 2020 May 11;61(5):28
pubmed: 32421148
Biol Open. 2020 Aug 25;9(8):
pubmed: 32747447
Int J Biochem Cell Biol. 2015 Apr;61:45-52
pubmed: 25660369
Front Pharmacol. 2018 Jul 18;9:787
pubmed: 30072901
Methods Mol Biol. 2017;1647:255-266
pubmed: 28809009
Bioinformatics. 2012 Nov 15;28(22):3002-3
pubmed: 22962344
J Chem Inf Model. 2015 Nov 23;55(11):2324-37
pubmed: 26479676
Ther Adv Ophthalmol. 2021 Feb 27;13:2515841421997191
pubmed: 33738427
Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3060-6
pubmed: 16123402
BJU Int. 2004 Jun;93(9):1276-81
pubmed: 15180622
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
J Biol Chem. 2003 Apr 18;278(16):14442-14450
pubmed: 12566452
J Biol Chem. 2015 Aug 7;290(32):19743-55
pubmed: 26092729
Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14386-14394
pubmed: 32513693
Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082
pubmed: 29126136
Tumour Biol. 2016 Jan;37(1):931-42
pubmed: 26260271
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4619-30
pubmed: 26200502
Cochrane Database Syst Rev. 2019 Jan 31;1:CD012621
pubmed: 30701543
Curr Med Chem. 2021;28(12):2418-2437
pubmed: 32964819