Finding New Molecular Targets of Familiar Natural Products Using In Silico Target Prediction.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
26 Sep 2020
Historique:
received: 01 09 2020
revised: 19 09 2020
accepted: 21 09 2020
entrez: 30 9 2020
pubmed: 1 10 2020
medline: 26 2 2021
Statut: epublish

Résumé

Natural products comprise a rich reservoir for innovative drug leads and are a constant source of bioactive compounds. To find pharmacological targets for new or already known natural products using modern computer-aided methods is a current endeavor in drug discovery. Nature's treasures, however, could be used more effectively. Yet, reliable pipelines for the large-scale target prediction of natural products are still rare. We developed an in silico workflow consisting of four independent, stand-alone target prediction tools and evaluated its performance on dihydrochalcones (DHCs)-a well-known class of natural products. Thereby, we revealed four previously unreported protein targets for DHCs, namely 5-lipoxygenase, cyclooxygenase-1, 17β-hydroxysteroid dehydrogenase 3, and aldo-keto reductase 1C3. Moreover, we provide a thorough strategy on how to perform computational target predictions and guidance on using the respective tools.

Identifiants

pubmed: 32993084
pii: ijms21197102
doi: 10.3390/ijms21197102
pmc: PMC7582679
pii:
doi:

Substances chimiques

Biological Products 0
Enzyme Inhibitors 0
Oxidoreductases EC 1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : GECT Euregio Tirol-Südtirol-Trentino
ID : IPN55
Organisme : Austrian Science Fund
ID : T-942

Références

J Steroid Biochem Mol Biol. 2011 May;125(1-2):148-61
pubmed: 21300150
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Nucleic Acids Res. 2019 Jul 2;47(W1):W357-W364
pubmed: 31106366
Nature. 2012 Jun 10;486(7403):361-7
pubmed: 22722194
J Comput Aided Mol Des. 2006 Dec;20(12):773-88
pubmed: 17051340
J Mol Biol. 1990 Oct 5;215(3):403-10
pubmed: 2231712
Nat Rev Drug Discov. 2004 Aug;3(8):673-83
pubmed: 15286734
Planta Med. 2009 Feb;75(3):195-204
pubmed: 19096995
Nucleic Acids Res. 2019 Jan 8;47(D1):D1102-D1109
pubmed: 30371825
Prog Chem Org Nat Prod. 2019;110:177-238
pubmed: 31621014
Nat Chem. 2014 Dec;6(12):1072-8
pubmed: 25411885
Nature. 2009 Nov 12;462(7270):175-81
pubmed: 19881490
Methods Mol Biol. 2017;1558:3-39
pubmed: 28150231
Phytochemistry. 2013 Jun;90:78-89
pubmed: 23562371
J Nat Prod. 2016 Mar 25;79(3):629-61
pubmed: 26852623
Life Sci. 2001 Jan 5;68(7):751-61
pubmed: 11205867
Br J Pharmacol. 2014 May;171(9):2399-412
pubmed: 24467325
Nat Biotechnol. 2007 Feb;25(2):197-206
pubmed: 17287757
Drug Discov Today Technol. 2010 Winter;7(4):e203-70
pubmed: 24103796
Nucleic Acids Res. 2012 Jan;40(Database issue):D1113-7
pubmed: 22067455
J Med Chem. 2008 Mar 13;51(5):1145-9
pubmed: 18260618
J Med Chem. 2010 Jul 8;53(13):4891-905
pubmed: 20540517
J Chem Inf Model. 2006 Sep-Oct;46(5):2146-57
pubmed: 16995745
Front Physiol. 2018 Nov 21;9:1575
pubmed: 30519189
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18787-92
pubmed: 20956335
Methods. 2015 Jan;71:98-103
pubmed: 25277948
J Med Chem. 2005 Dec 15;48(25):7946-59
pubmed: 16335919
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W55-9
pubmed: 18499712
Drug Discov Today. 2014 Dec;19(12):1871-82
pubmed: 25172801
Nat Chem. 2016 Jun;8(6):531-41
pubmed: 27219696
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W26-31
pubmed: 24878925
J Comput Aided Mol Des. 2010 Sep;24(9):789-801
pubmed: 20614163
Angew Chem Int Ed Engl. 2015 Sep 1;54(36):10516-20
pubmed: 26202212
J Med Chem. 2010 Dec 23;53(24):8461-7
pubmed: 20929257
J Pharmacol Exp Ther. 2008 Sep;326(3):975-82
pubmed: 18550688
J Endocrinol. 2007 Dec;195(3):459-72
pubmed: 18000308
Arch Biochem Biophys. 2000 Jun 15;378(2):321-32
pubmed: 10860549
Biochem Pharmacol. 2018 Jun;152:45-59
pubmed: 29551587
Cell Commun Signal. 2020 Jan 24;18(1):11
pubmed: 31980029
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Heart Fail Rev. 2020 May;25(3):537-548
pubmed: 31705352
Br J Clin Pharmacol. 2007 Nov;64(5):563-5
pubmed: 17935601
J Med Chem. 2005 Mar 10;48(5):1489-95
pubmed: 15743191
J Biochem. 1998 Nov;124(5):940-6
pubmed: 9792917
Oncol Rep. 2012 Sep;28(3):797-805
pubmed: 22710558
Diabetol Metab Syndr. 2018 Dec 18;10:93
pubmed: 30574207
Prostate. 2002 Sep 15;53(1):65-8
pubmed: 12210481
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W32-8
pubmed: 24792161
Nucleic Acids Res. 2012 Jan;40(Database issue):D1100-7
pubmed: 21948594
J Steroid Biochem Mol Biol. 2011 May;125(1-2):129-42
pubmed: 21236343
Drug Discov Today. 2008 Oct;13(19-20):894-901
pubmed: 18691670
Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954
pubmed: 27899562
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6740-4
pubmed: 19836949
Nucleic Acids Res. 2008 Jan;36(Database issue):D919-22
pubmed: 17942422
J Med Chem. 2011 Nov 10;54(21):7547-57
pubmed: 21972996
Bioinformatics. 2013 Dec 1;29(23):3073-9
pubmed: 24048355
Anal Biochem. 1988 Feb 15;169(1):71-80
pubmed: 3369689
J Biomol Screen. 2005 Jun;10(4):374-82
pubmed: 15964939
J Nat Prod. 2019 Jan 25;82(1):136-147
pubmed: 30629444
J Clin Med. 2019 Nov 01;8(11):
pubmed: 31683785
Methods Enzymol. 1991;206:477-83
pubmed: 1784232
Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201
pubmed: 17145705
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
Nat Rev Drug Discov. 2005 Mar;4(3):206-20
pubmed: 15729362
J Chem Inf Model. 2008 Apr;48(4):755-65
pubmed: 18335977
Clin Pharmacol Ther. 2013 Apr;93(4):335-41
pubmed: 23443757
Drug Discov Today. 2018 Feb;23(2):219-234
pubmed: 29031621
Mol Endocrinol. 2001 Nov;15(11):2010-20
pubmed: 11682630
Front Pharmacol. 2017 Aug 25;8:580
pubmed: 28970799
Pharmacol Rev. 2013 Dec 31;66(1):334-95
pubmed: 24381236
J Med Chem. 2002 May 23;45(11):2213-21
pubmed: 12014959
Mol Endocrinol. 2007 Oct;21(10):2579-95
pubmed: 17595315
J Chem Inf Model. 2019 May 28;59(5):1728-1742
pubmed: 30817146
Mol Cell Endocrinol. 2009 Mar 25;301(1-2):259-65
pubmed: 18775469
J Chem Inf Model. 2016 Apr 25;56(4):747-62
pubmed: 26882208

Auteurs

Fabian Mayr (F)

Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Gabriele Möller (G)

Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.

Ulrike Garscha (U)

Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University Greifswald, Friedrich-Ludwig-Jahn-Straße 17, 17489 Greifswald, Germany.

Jana Fischer (J)

Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University Greifswald, Friedrich-Ludwig-Jahn-Straße 17, 17489 Greifswald, Germany.

Patricia Rodríguez Castaño (P)

Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital Bern, Freiburgstrasse 15, 3010 Bern, Switzerland.
Department of Biomedical Research, University of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland.

Silvia G Inderbinen (SG)

Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Veronika Temml (V)

Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Birgit Waltenberger (B)

Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Stefan Schwaiger (S)

Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Rolf W Hartmann (RW)

Helmholtz Institute of Pharmaceutical Research Saarland (HIPS), Department for Drug Design and Optimization, Campus E8.1, 66123 Saarbrücken, Germany.
Saarland University, Pharmaceutical and Medicinal Chemistry, Campus E8.1, 66123 Saarbrücken, Germany.

Christian Gege (C)

University of Heidelberg, Institute of Pharmacy and Molecular Biotechnology (IPMB), Medicinal Chemistry, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

Stefan Martens (S)

Research and Innovation Centre, Fondazione Edmund Mach (FEM), Via Mach 1, 38010 San Michele all'Adige, Italy.

Alex Odermatt (A)

Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Amit V Pandey (AV)

Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital Bern, Freiburgstrasse 15, 3010 Bern, Switzerland.
Department of Biomedical Research, University of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland.

Oliver Werz (O)

Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany.

Jerzy Adamski (J)

Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
Lehrstuhl für Experimentelle Genetik, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85356 Freising-Weihenstephan, Germany.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.

Hermann Stuppner (H)

Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Daniela Schuster (D)

Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Paracelsus Medical University Salzburg, Strubergasse 21, 5020 Salzburg, Austria.
Institute of Pharmacy/Pharmaceutical Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH