دورية أكاديمية
AMALPHI: A Machine Learning Platform for Predicting Drug-Induced PhospholIpidosis.
| العنوان: | AMALPHI: A Machine Learning Platform for Predicting Drug-Induced PhospholIpidosis. |
|---|---|
| المؤلفون: | Lomuscio MC; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy., Abate C; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy.; Department of Pharmacy-Pharmaceutical Sciences, University of the Studies of Bari 'Aldo Moro', Via E.Orabona 4, 70125 Bari, Italy., Alberga D; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy., Laghezza A; Department of Pharmacy-Pharmaceutical Sciences, University of the Studies of Bari 'Aldo Moro', Via E.Orabona 4, 70125 Bari, Italy., Corriero N; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy., Colabufo NA; Department of Pharmacy-Pharmaceutical Sciences, University of the Studies of Bari 'Aldo Moro', Via E.Orabona 4, 70125 Bari, Italy., Saviano M; CNR─Institute of Crystallography, Via Vivaldi 43, 81100 Caserta, Italy., Delre P; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy., Mangiatordi GF; CNR─Institute of Crystallography, Via Amendola 122/o, 70126 Bari, Italy. |
| المصدر: | Molecular pharmaceutics [Mol Pharm] 2024 Feb 05; Vol. 21 (2), pp. 864-872. Date of Electronic Publication: 2023 Dec 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2004- |
| مواضيع طبية MeSH: | Phospholipids* , Lipidoses*/chemically induced, Humans ; Hep G2 Cells ; Lysosomes ; Machine Learning ; Antiviral Agents/adverse effects |
| مستخلص: | Drug-induced phospholipidosis (PLD) involves the accumulation of phospholipids in cells of multiple tissues, particularly within lysosomes, and it is associated with prolonged exposure to druglike compounds, predominantly cationic amphiphilic drugs (CADs). PLD affects a significant portion of drugs currently in development and has recently been proven to be responsible for confounding antiviral data during drug repurposing for SARS-CoV-2. In these scenarios, it has become crucial to identify potential safe drug candidates in advance and distinguish them from those that may lead to false in vitro antiviral activity. In this work, we developed a series of machine learning classifiers with the aim of predicting the PLD-inducing potential of drug candidates. The models were built on a high-quality chemical collection comprising 545 curated small molecules extracted from ChEMBL v30. The most effective model, obtained using the balanced random forest algorithm, achieved high performance, including an AUC value computed in validation as high as 0.90. The model was made freely available through a user-friendly web platform named AMALPHI (https://www.ba.ic.cnr.it/softwareic/amalphiportal/), which can represent a valuable tool for medicinal chemists interested in conducting an early evaluation of PLD inducer potential. |
| References: | Mol Pharm. 2010 Oct 4;7(5):1708-14. (PMID: 20799726) Expert Opin Drug Saf. 2006 Jul;5(4):567-83. (PMID: 16774494) J Chem Inf Model. 2013 Jun 24;53(6):1436-46. (PMID: 23692521) Bioinformatics. 2017 Nov 15;33(22):3658-3660. (PMID: 28961788) Mol Pharm. 2017 Dec 4;14(12):4346-4352. (PMID: 29077420) Med Res Rev. 2022 Mar;42(2):744-769. (PMID: 34697818) Comput Biol Med. 2023 Sep;164:107314. (PMID: 37572442) J Cheminform. 2012 Jan 26;4:2. (PMID: 22281160) J Chem Inf Model. 2022 Mar 28;62(6):1411-1424. (PMID: 35294184) Cell Biol Toxicol. 2003 Jun;19(3):161-76. (PMID: 12945744) Nature. 2020 Jul;583(7816):459-468. (PMID: 32353859) Toxicol Sci. 2006 Mar;90(1):133-41. (PMID: 16338956) Biochemistry. 1985 Nov 5;24(23):6515-20. (PMID: 4084534) Front Cell Infect Microbiol. 2023 Aug 11;13:1100028. (PMID: 37637460) Science. 2021 Jul 30;373(6554):541-547. (PMID: 34326236) Sci Rep. 2023 Aug 7;13(1):12798. (PMID: 37550340) Cell Biol Toxicol. 2006 Jan;22(1):15-27. (PMID: 16463016) Front Pharmacol. 2022 Sep 05;13:951083. (PMID: 36133824) Biochem Pharmacol. 1978;27(8):1103-8. (PMID: 358990) J Cheminform. 2020 Jun 12;12(1):43. (PMID: 33431010) Antimicrob Agents Chemother. 2020 Jul 22;64(8):. (PMID: 32513799) J Chem Inf Model. 2021 Sep 27;61(9):4125-4130. (PMID: 34516123) Toxicol Sci. 2005 Feb;83(2):282-92. (PMID: 15342952) J Chem Inf Model. 2014 Aug 25;54(8):2224-32. (PMID: 25062434) Toxicol Sci. 2007 Mar;96(1):101-14. (PMID: 17175557) Biol Chem. 2019 Dec 18;401(1):31-46. (PMID: 31408430) Biochem Pharmacol. 2001 Dec 15;62(12):1661-73. (PMID: 11755120) Toxicol Mech Methods. 2008;18(2-3):217-27. (PMID: 20020916) J Toxicol Pathol. 2010 Dec;23(4):213-34. (PMID: 22272032) Biochem Pharmacol. 1984 May 15;33(10):1639-44. (PMID: 6732837) Chem Biol Drug Des. 2010 Nov;76(5):397-406. (PMID: 20925691) CRC Crit Rev Toxicol. 1975 Nov;4(2):185-218. (PMID: 2448) Mol Inform. 2012 Oct;31(10):725-39. (PMID: 27476455) J Cheminform. 2013 May 21;5:24. (PMID: 23694746) |
| فهرسة مساهمة: | Keywords: SARS-CoV-2; ligand-based classifiers; machine learning; phospholipidosis |
| المشرفين على المادة: | 0 (Phospholipids) 0 (Antiviral Agents) |
| تواريخ الأحداث: | Date Created: 20231222 Date Completed: 20240206 Latest Revision: 20240211 |
| رمز التحديث: | 20240211 |
| مُعرف محوري في PubMed: | PMC10853961 |
| DOI: | 10.1021/acs.molpharmaceut.3c00964 |
| PMID: | 38134445 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1543-8392 |
|---|---|
| DOI: | 10.1021/acs.molpharmaceut.3c00964 |