دورية أكاديمية
أعرض في EDS

Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily.

التفاصيل البيبلوغرافية
العنوان: Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily.
المؤلفون: Digles D; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Ingles-Prieto A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Dvorak V; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Mocking TAM; Division of Drug Discovery and Safety, LACDR, Leiden University, Leiden, Netherlands., Goldmann U; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Garofoli A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Homan EJ; Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Di Silvio A; Axxam SpA, Bresso, Italy., Azzollini L; Axxam SpA, Bresso, Italy., Sassone F; Axxam SpA, Bresso, Italy., Fogazza M; Axxam SpA, Bresso, Italy., Bärenz F; Sanofi, Integrated Drug Discovery, Industriepark Hoechst, Frankfurt am Main, Hessen, Germany., Pommereau A; Sanofi, Integrated Drug Discovery, Industriepark Hoechst, Frankfurt am Main, Hessen, Germany., Zuschlag Y; Sanofi, Integrated Drug Discovery, Industriepark Hoechst, Frankfurt am Main, Hessen, Germany., Ooms JF; Division of Drug Discovery and Safety, LACDR, Leiden University, Leiden, Netherlands., Tranberg-Jensen J; Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Hansen JS; Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Stanka J; Lead Identification and Characterization, Bayer Pharmaceuticals, Wuppertal, Germany., Sijben HJ; Division of Drug Discovery and Safety, LACDR, Leiden University, Leiden, Netherlands., Batoulis H; Lead Identification and Characterization, Bayer Pharmaceuticals, Wuppertal, Germany., Bender E; Lead Identification and Characterization, Bayer Pharmaceuticals, Wuppertal, Germany., Martini R; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., IJzerman AP; Division of Drug Discovery and Safety, LACDR, Leiden University, Leiden, Netherlands., Sauer DB; Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Heitman LH; Division of Drug Discovery and Safety, LACDR, Leiden University, Leiden, Netherlands., Manolova V; CSL Vifor, StGallen, Switzerland., Reinhardt J; Novartis Pharma AG, Basel, Switzerland., Ehrmann A; Lead Identification and Characterization, Bayer Pharmaceuticals, Wuppertal, Germany., Leippe P; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Ecker GF; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Huber KVM; Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Licher T; Sanofi, Integrated Drug Discovery, Industriepark Hoechst, Frankfurt am Main, Hessen, Germany., Scarabottolo L; Axxam SpA, Bresso, Italy., Wiedmer T; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Superti-Furga G; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.; Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
المصدر: Frontiers in pharmacology [Front Pharmacol] 2024 Jul 09; Vol. 15, pp. 1401599. Date of Electronic Publication: 2024 Jul 09 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Media]
مستخلص: With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs.
Competing Interests: AS, LA, FS, MF, and LS are employees of Axxam SpA. JS, HB, EB, and AE are employees of Bayer Pharmaceuticals. VM is an employee of CSL Vifor. JR is an employee of Novartis Pharma AG. GS-F is co-founder and own shares of Solgate GmbH, and SLC-focused company. FB, AP, YZ, and TL are employees of Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Digles, Ingles-Prieto, Dvorak, Mocking, Goldmann, Garofoli, Homan, Di Silvio, Azzollini, Sassone, Fogazza, Bärenz, Pommereau, Zuschlag, Ooms, Tranberg-Jensen, Hansen, Stanka, Sijben, Batoulis, Bender, Martini, IJzerman, Sauer, Heitman, Manolova, Reinhardt, Ehrmann, Leippe, Ecker, Huber, Licher, Scarabottolo, Wiedmer and Superti-Furga.)
References: Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4155-60. (PMID: 9108121)
J Med Chem. 2020 Apr 23;63(8):3834-3867. (PMID: 31774679)
Nat Chem Biol. 2024 May;20(5):577-585. (PMID: 37904048)
Biotechniques. 2019 Apr;66(4):167-170. (PMID: 30987442)
Nat Rev Drug Discov. 2017 Jan;16(1):19-34. (PMID: 27910877)
Front Pharmacol. 2022 May 23;13:872335. (PMID: 35677430)
Nat Genet. 2019 Nov;51(11):1596-1606. (PMID: 31676859)
Int J Mol Sci. 2022 Jan 21;23(3):. (PMID: 35163125)
Mol Syst Biol. 2020 Jul;16(7):e9652. (PMID: 32697042)
J Vis Exp. 2023 Sep 29;(199):. (PMID: 37843272)
J Biomol Screen. 1999;4(2):67-73. (PMID: 10838414)
Int J Mol Sci. 2023 Jan 20;24(3):. (PMID: 36768423)
Expert Opin Drug Discov. 2023 Jul-Dec;18(10):1099-1115. (PMID: 37563933)
J Med Chem. 2010 Apr 8;53(7):2719-40. (PMID: 20131845)
Nutr Neurosci. 2008 Dec;11(6):244-50. (PMID: 19000377)
Nucleic Acids Res. 2021 Jan 8;49(D1):D1334-D1346. (PMID: 33156327)
Nucleic Acids Res. 2023 Jan 6;51(D1):D523-D531. (PMID: 36408920)
J Struct Biol. 2010 Oct;172(1):85-93. (PMID: 20394823)
Cell. 2015 Jul 30;162(3):478-87. (PMID: 26232220)
J Chem Inf Model. 2023 Mar 27;63(6):1745-1755. (PMID: 36926886)
Mol Aspects Med. 2013 Apr-Jun;34(2-3):373-85. (PMID: 23506878)
Nat Rev Drug Discov. 2010 Mar;9(3):215-36. (PMID: 20190787)
BMC Bioinformatics. 2015 May 22;16:169. (PMID: 25994840)
Sci Rep. 2021 Jun 10;11(1):12290. (PMID: 34112854)
Nat Rev Drug Discov. 2020 Jul;19(7):429-430. (PMID: 32265506)
J Neurochem. 2001 Oct;79(2):297-302. (PMID: 11677257)
BMC Bioinformatics. 2011 Apr 12;12:94. (PMID: 21486481)
Cell Mol Life Sci. 2021 Dec 31;79(1):20. (PMID: 34971415)
Eur J Drug Metab Pharmacokinet. 2021 Sep;46(5):625-635. (PMID: 34275128)
Mol Cell. 2021 Sep 16;81(18):3731-3748. (PMID: 34547236)
Nucleic Acids Res. 2015 Jul 1;43(W1):W612-20. (PMID: 25883136)
Endocr Rev. 2019 Aug 1;40(4):1092-1107. (PMID: 30901029)
Chem Rev. 2021 May 12;121(9):5289-5335. (PMID: 33886296)
Medchemcomm. 2016 Jun 1;7(6):1069-1081. (PMID: 27672436)
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26. (PMID: 11259830)
Curr Protoc. 2023 Mar;3(3):e650. (PMID: 36912603)
Nat Rev Drug Discov. 2018 May;17(5):317-332. (PMID: 29472638)
Methods Enzymol. 2015;556:373-83. (PMID: 25857791)
Eur J Med Chem. 2022 Feb 5;229:114092. (PMID: 34998055)
Trends Biochem Sci. 2023 Sep;48(9):801-814. (PMID: 37355450)
J Med Chem. 2023 Jun 8;66(11):7101-7139. (PMID: 37224022)
Nat Rev Drug Discov. 2016 Feb;15(2):143. (PMID: 26837595)
Mol Aspects Med. 2013 Apr-Jun;34(2-3):719-34. (PMID: 23506905)
J Cheminform. 2013 Jan 14;5(1):3. (PMID: 23317286)
ACS Med Chem Lett. 2015 Jan 28;6(3):244-8. (PMID: 25815140)
Nucleic Acids Res. 2019 Jan 8;47(D1):D930-D940. (PMID: 30398643)
Methods Mol Biol. 2020;2168:73-103. (PMID: 33582988)
Biochem Pharmacol. 2020 Feb;172:113747. (PMID: 31830468)
Mol Aspects Med. 2013 Apr-Jun;34(2-3):95-107. (PMID: 23506860)
Nucleic Acids Res. 2018 Jul 2;46(W1):W563-W570. (PMID: 29718389)
Bioorg Med Chem. 2018 May 1;26(8):1614-1627. (PMID: 29456112)
Sci Rep. 2021 Jan 14;11(1):1312. (PMID: 33446713)
Biochem Pharmacol. 2016 Oct 15;118:31-39. (PMID: 27521504)
Front Pharmacol. 2021 Aug 10;12:722889. (PMID: 34447313)
Biosens Bioelectron. 2022 Feb 1;197:113763. (PMID: 34768066)
Nat Chem Biol. 2020 Apr;16(4):469-478. (PMID: 32152546)
Biometals. 2023 Feb;36(1):227-237. (PMID: 36454509)
ChemMedChem. 2016 Oct 19;11(20):2261-2271. (PMID: 27552707)
Trends Pharmacol Sci. 2022 May;43(5):358-361. (PMID: 35232590)
Biochem Pharmacol. 2004 Jun 1;67(11):2115-27. (PMID: 15135308)
Nature. 2007 Feb 22;445(7130):881-5. (PMID: 17293876)
Molecules. 2023 Jan 24;28(3):. (PMID: 36770817)
Cell Chem Biol. 2024 May 20;:. (PMID: 38806058)
iScience. 2022 Sep 08;25(10):105096. (PMID: 36164651)
Nat Rev Drug Discov. 2015 Aug;14(8):543-60. (PMID: 26111766)
FEBS J. 2021 May;288(9):2784-2835. (PMID: 32810346)
Clin Pharmacol Ther. 2022 Sep;112(3):439-442. (PMID: 35938294)
Mol Cell Biochem. 2022 Apr;477(4):1207-1216. (PMID: 35084672)
Nucleic Acids Res. 2022 Jan 7;50(D1):D1282-D1294. (PMID: 34718737)
Mol Inform. 2011 Oct;30(10):847-50. (PMID: 27468104)
Sci Rep. 2022 Aug 2;12(1):13248. (PMID: 35918457)
J Membr Biol. 2016 Jun;249(3):239-49. (PMID: 26690923)
Curr Opin Chem Biol. 2021 Jun;62:53-63. (PMID: 33689964)
Nucleic Acids Res. 2023 Jan 6;51(D1):D1492-D1502. (PMID: 36268860)
Nat Metab. 2023 Aug;5(8):1319-1336. (PMID: 37537371)
فهرسة مساهمة: Keywords: KNIME; solute carrier; tool compound; transport assay; transport protein
تواريخ الأحداث: Date Created: 20240725 Latest Revision: 20240726
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC11267547
DOI: 10.3389/fphar.2024.1401599
PMID: 39050757
قاعدة البيانات: MEDLINE
الوصف
تدمد:1663-9812
DOI:10.3389/fphar.2024.1401599