Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.
Hit compound generation
Molecular dynamics simulation
Skin cancer
Systems genetics
Journal
Journal of molecular graphics & modelling
ISSN: 1873-4243
Titre abrégé: J Mol Graph Model
Pays: United States
ID NLM: 9716237
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
23
02
2023
revised:
03
06
2023
accepted:
05
06
2023
pmc-release:
01
11
2024
medline:
14
8
2023
pubmed:
19
6
2023
entrez:
18
6
2023
Statut:
ppublish
Résumé
Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARβ). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.
Identifiants
pubmed: 37331258
pii: S1093-3263(23)00137-7
doi: 10.1016/j.jmgm.2023.108539
pmc: PMC10529808
mid: NIHMS1910292
pii:
doi:
Substances chimiques
retinoic acid receptor beta
0
Receptors, Histamine H1
0
Receptors, Retinoic Acid
0
Histamine Antagonists
0
Histamine H1 Antagonists
0
Alitretinoin
1UA8E65KDZ
Tretinoin
5688UTC01R
Types de publication
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108539Subventions
Organisme : NIAMS NIH HHS
ID : T32 AR007411
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interest.
Références
J Dermatolog Treat. 2016;27(1):54-8
pubmed: 25886084
Neurotherapeutics. 2009 Jan;6(1):78-85
pubmed: 19110200
Oncogene. 2001 Apr 30;20(19):2365-77
pubmed: 11402333
Adv Cancer Res. 1987;49:29-52
pubmed: 2823543
Clin Cancer Res. 2018 Oct 15;24(20):5085-5097
pubmed: 30084838
J Mol Graph Model. 2018 Jan;79:166-174
pubmed: 29197725
Int J Mol Sci. 2020 Feb 07;21(3):
pubmed: 32046099
Mol Vis. 2013 Aug 06;19:1795-803
pubmed: 23946634
J Nutr. 2002 Dec;132(12):3809S-3813S
pubmed: 12468629
J Cell Physiol. 2013 Aug;228(8):1676-87
pubmed: 23359405
J Cancer Res Clin Oncol. 1988;114(6):588-92
pubmed: 3204106
Ann Palliat Med. 2016 Oct;5(4):298-302
pubmed: 27701876
J Biomol Struct Dyn. 1998 Dec;16(3):671-82
pubmed: 10052623
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D449-51
pubmed: 14681454
J Mol Graph Model. 2019 Jun;89:122-130
pubmed: 30884449
Pharmacol Res. 2022 Oct;184:106398
pubmed: 35988867
Pharmaceuticals (Basel). 2021 Aug 31;14(9):
pubmed: 34577587
Mol Cell Biol. 2003 Apr;23(8):2844-58
pubmed: 12665583
Methods Mol Biol. 2017;1488:75-120
pubmed: 27933521
Nucleic Acids Res. 2013 Jan;41(Database issue):D1228-33
pubmed: 23180781
J Exp Clin Cancer Res. 2016 Jun 24;35(1):101
pubmed: 27342319
Biomed Res Int. 2015;2015:538019
pubmed: 25866791
Bioorg Med Chem Lett. 2016 Jul 15;26(14):3274-3277
pubmed: 27261179
Neuropharmacology. 2012 Aug;63(2):280-91
pubmed: 22507664
Compr Ther. 1984 May;10(5):48-54
pubmed: 6145539
Biophys J. 2003 Aug;85(2):1176-85
pubmed: 12885661
N Engl J Med. 1995 May 4;332(18):1181-5
pubmed: 7700310
Cancer Res. 2002 May 1;62(9):2455-61
pubmed: 11980632
Nat Commun. 2012;3:1079
pubmed: 23011133
Methods Mol Biol. 2012;857:231-57
pubmed: 22323224
J Am Chem Soc. 2014 Oct 15;136(41):14554-9
pubmed: 25229711
Metabolism. 2009 Jun;58(6):867-70
pubmed: 19375125
Nature. 1992 Jan 30;355(6359):446-9
pubmed: 1310351
Sci Rep. 2015 Nov 26;5:17209
pubmed: 26607293
J Virol. 2006 Jul;80(13):6411-9
pubmed: 16775329
Cell. 2012 Sep 14;150(6):1287-99
pubmed: 22939713
Med Res Rev. 2006 Jul;26(4):397-413
pubmed: 16450343
JAMA. 1962 Jul 28;181:290-4
pubmed: 14488364
Cells. 2018 Aug 23;7(9):
pubmed: 30142927
Science. 1992 Dec 18;258(5090):1944-6
pubmed: 1335166
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D452-5
pubmed: 14681455
Int J Cancer. 2014 Nov 15;135(10):2262-72
pubmed: 25130873
Nature. 2013 May 23;497(7450):451-7
pubmed: 23698443
Breast. 2005 Jun;14(3):236-41
pubmed: 15927833
J Phys Chem B. 2014 Sep 18;118(37):10874-81
pubmed: 25166278
EMBO Rep. 2004 Sep;5(9):877-82
pubmed: 15319780
Ann Intern Med. 1982 Jun;96(6 Pt 1):693-700
pubmed: 6283973
Cancer Rep (Hoboken). 2020 Dec;3(6):e1284
pubmed: 32881426
Proteins. 2011 Oct;79(10):2794-812
pubmed: 21905107
Molecules. 2017 Jan 17;22(1):
pubmed: 28106755
Exp Cell Res. 2004 Jul 1;297(1):68-81
pubmed: 15194426
J Chem Inf Model. 2008 Mar;48(3):489-97
pubmed: 18302357
Dermatol Ther (Heidelb). 2021 Jun;11(3):719-732
pubmed: 33846906
Nature. 1995 Dec 14;378(6558):681-9
pubmed: 7501014
Crit Rev Oncol Hematol. 2002 Jan;41(1):41-55
pubmed: 11796231
J Acquir Immune Defic Syndr (1988). 1991;4(9):839-46
pubmed: 1895204
Science. 2016 Jun 10;352(6291):aad0189
pubmed: 27284200
Allergy. 2000;55 Suppl 64:17-27
pubmed: 11291777
Arch Dermatol. 2000 Dec;136(12):1461-9
pubmed: 11115156
J Chem Theory Comput. 2019 Mar 12;15(3):1863-1874
pubmed: 30768902
Nucleic Acids Res. 2015 Jan;43(Database issue):D470-8
pubmed: 25428363
Pharmaceuticals (Basel). 2021 Sep 03;14(9):
pubmed: 34577596
PLoS One. 2015 May 11;10(5):e0125829
pubmed: 25961853
Trends Pharmacol Sci. 2008 Jun;29(6):314-21
pubmed: 18471899
Expert Opin Drug Discov. 2015 May;10(5):449-61
pubmed: 25835573
Nat Protoc. 2015 Jun;10(6):823-44
pubmed: 25950236
Antibiotics (Basel). 2021 Apr 21;10(5):
pubmed: 33919115
J Chem Inf Model. 2019 Mar 25;59(3):1050-1061
pubmed: 30808172
Front Mol Biosci. 2020 Oct 30;7:587997
pubmed: 33195435
Blood. 2018 May 3;131(18):2007-2015
pubmed: 29514782
J Mammary Gland Biol Neoplasia. 2001 Apr;6(2):193-201
pubmed: 11501579
J Clin Oncol. 1988 May;6(5):863-7
pubmed: 3367189
Nucleic Acids Res. 2012 Jan;40(Database issue):D857-61
pubmed: 22096227
PLoS Pathog. 2021 Jan 20;17(1):e1009179
pubmed: 33471866
Nat Commun. 2016 Feb 02;7:10464
pubmed: 26833085
BMC Genet. 2004 Apr 29;5:7
pubmed: 15117419
Med Clin North Am. 1997 Mar;81(2):471-94
pubmed: 9093238
Molecules. 2018 Apr 28;23(5):
pubmed: 29710787
Elife. 2015 Dec 23;4:
pubmed: 26701914
Adv Pharm Bull. 2015 Sep;5(3):305-13
pubmed: 26504751
Nat Genet. 2005 Mar;37(3):233-42
pubmed: 15711545
Expert Opin Pharmacother. 2013 Dec;14(18):2553-69
pubmed: 24191914
J Comput Chem. 2011 Apr 15;32(5):866-77
pubmed: 20949517
Cancer. 1989 Dec 15;64(12):2424-30
pubmed: 2819653
Cells. 2018 Sep 07;7(9):
pubmed: 30205516
J Am Chem Soc. 2012 Jul 25;134(29):12043-53
pubmed: 22612276
J Chromatogr A. 2011 Sep 16;1218(37):6356-68
pubmed: 21820118
Methods Mol Biol. 2017;1647:255-266
pubmed: 28809009
Nat Commun. 2017 Oct 11;8(1):868
pubmed: 29021580
J Comput Aided Mol Des. 2007 Dec;21(12):681-91
pubmed: 17899391
Database (Oxford). 2011 Jan 12;2011:baq037
pubmed: 21233089
J Clin Psychiatry. 2002 Nov;63(11):1020-7
pubmed: 12444816
Protein Sci. 1997 Jun;6(6):1293-301
pubmed: 9194189
Acc Chem Res. 2000 Dec;33(12):889-97
pubmed: 11123888
Biochem J. 2002 Sep 1;366(Pt 2):459-69
pubmed: 12027803
Nat Struct Biol. 1998 Mar;5(3):199-202
pubmed: 9501913
Transl Gastrointest Cancer. 2012 Oct;1(3):215-227
pubmed: 24639917
Annu Rev Med. 2007;58:491-504
pubmed: 17052163
J Am Acad Dermatol. 1993 Jan;28(1):61-5
pubmed: 8381146
Cancer Cell. 2022 Jan 10;40(1):36-52.e9
pubmed: 34822775
EMBO J. 2000 Jun 1;19(11):2592-601
pubmed: 10835357
Nat Rev Cancer. 2001 Dec;1(3):181-93
pubmed: 11902573
J Mol Graph Model. 2013 Nov;46:41-51
pubmed: 24121518
Int J Mol Sci. 2020 Nov 11;21(22):
pubmed: 33187070
Dermatologica. 1987;174(3):150-1
pubmed: 3556707
Proteins. 2005 Dec 1;61(4):704-21
pubmed: 16231289
Drugs Aging. 1995 Jun;6(6):479-96
pubmed: 7663068