دورية أكاديمية
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Hybrid In Silico and TR-FRET-Guided Discovery of Novel BCL-2 Inhibitors.

التفاصيل البيبلوغرافية
العنوان: Hybrid In Silico and TR-FRET-Guided Discovery of Novel BCL-2 Inhibitors.
المؤلفون: Sahin K; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34353, Turkey., Orhan MD; Neuroscience Program, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey.; Neuroscience Laboratory, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey., Avsar T; Neuroscience Program, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey.; Neuroscience Laboratory, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey.; Department of Medical Biology, School of Medicine, Bahcesehir University, Istanbul 34353, Turkey., Durdagi S; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34353, Turkey.; Neuroscience Program, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey.; Neuroscience Laboratory, Health Sciences Institute, Bahcesehir University, Istanbul 34353, Turkey.; Virtual Drug Screening and Development Laboratory, School of Medicine, Bahcesehir University, Istanbul 34353, Turkey.
المصدر: ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2021 Apr 15; Vol. 4 (3), pp. 1111-1123. Date of Electronic Publication: 2021 Apr 15 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101721411 Publication Model: eCollection Cited Medium: Internet ISSN: 2575-9108 (Electronic) Linking ISSN: 25759108 NLM ISO Abbreviation: ACS Pharmacol Transl Sci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Chemical Society, [2018]-
مستخلص: B-Cell lymphoma 2 (BCL-2) regulates cell death in humans. In this study, combined multiscale in silico approaches and in vitro studies were employed. A small-molecule library that includes more than 210 000 compounds was used. The predicted therapeutic activity value (TAV) of the compounds in this library was computed with the binary cancer quantitative structure-activity relationships (QSAR) model. The molecules with a high calculated TAV were used in 26 individual toxicity QSAR models. As a result of this screening protocol, 288 nontoxic molecules with high predicted TAV were identified. These selected hits were then screened against the BCL-2 target protein using hybrid docking and molecular dynamics (MD) simulations. The interaction energies of identified compounds were compared with two known BCL-2 inhibitors. Then, the short MD simulations were carried out by initiating the best docking poses of 288 molecules. Average MM/GBSA energies were computed, and long MD simulations were employed to selected hits. The same calculations were also applied for two known BCL-2 inhibitors. Moreover, a five-site (AHRRR) structure-based pharmacophore model was constructed, and this model was used in the screening of the same database. On the basis of hybrid data-driven ligand identification study, final hits were selected and used in in vitro studies. Based on results of the time-resolved fluorescence resonance energy transfer (TR-FRET) analysis, further filtration was carried out for the U87-MG cell line tests. MTT cell proliferation assay analysis results showed that selected three potent compounds were significantly effective on glioma cells.
Competing Interests: The authors declare no competing financial interest.
(© 2021 American Chemical Society.)
References: Eur J Med Chem. 2017 Jul 7;134:159-184. (PMID: 28412530)
Cancer Res. 2008 May 1;68(9):3421-8. (PMID: 18451170)
Trends Biochem Sci. 2001 Jan;26(1):61-6. (PMID: 11165519)
Curr Comput Aided Drug Des. 2011 Jun;7(2):146-57. (PMID: 21534921)
Drug Discov Today. 2010 Jun;15(11-12):444-50. (PMID: 20362693)
Eur J Med Chem. 2015 Jan 7;89:207-51. (PMID: 25462241)
J Med Chem. 2006 Oct 5;49(20):5912-31. (PMID: 17004707)
Oncogene. 2002 Mar 27;21(13):1963-77. (PMID: 11960369)
Lancet Oncol. 2002 Aug;3(8):487-97. (PMID: 12147435)
J Histochem Cytochem. 2004 Jun;52(6):821-31. (PMID: 15150291)
CA Cancer J Clin. 2016 Jul;66(4):271-89. (PMID: 27253694)
BMC Chem. 2019 May 15;13(1):66. (PMID: 31384813)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
J Chem Inf Model. 2009 Oct;49(10):2356-68. (PMID: 19761201)
J Bioenerg Biomembr. 2000 Feb;32(1):35-46. (PMID: 11768760)
Nat Med. 2013 Feb;19(2):202-8. (PMID: 23291630)
J Chem Inf Model. 2005 Jan-Feb;45(1):160-9. (PMID: 15667141)
Front Chem. 2020 Apr 09;8:167. (PMID: 32328476)
BMC Bioinformatics. 2012;13 Suppl 17:S6. (PMID: 23282219)
CA Cancer J Clin. 2014 Jul-Aug;64(4):252-71. (PMID: 24890451)
Acta Pharmacol Sin. 2009 Dec;30(12):1694-708. (PMID: 19935678)
J Med Chem. 2006 Oct 19;49(21):6177-96. (PMID: 17034125)
Curr Med Chem. 2004 Nov;11(22):2991-3005. (PMID: 15544485)
J Am Chem Soc. 2004 Feb 4;126(4):1020-1. (PMID: 14746460)
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697. (PMID: 9895674)
J Biomol Struct Dyn. 2021 Feb;39(2):681-690. (PMID: 32048546)
Int J Mol Sci. 2019 Feb 16;20(4):. (PMID: 30781512)
J Med Chem. 2004 Mar 25;47(7):1739-49. (PMID: 15027865)
J Mol Graph Model. 2008 Jun;26(8):1237-51. (PMID: 18203638)
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. (PMID: 25559415)
Proteins. 2011 Oct;79(10):2794-812. (PMID: 21905107)
Biomed Pharmacother. 2015 Apr;71:37-45. (PMID: 25960213)
J Clin Oncol. 2000 Mar;18(5):1124-34. (PMID: 10694566)
J Med Chem. 2010 Dec 23;53(24):8461-7. (PMID: 20929257)
Clin Cancer Res. 2011 Mar 15;17(6):1394-404. (PMID: 21220478)
J Pharm Sci. 2008 Mar;97(3):1089-98. (PMID: 18214973)
Proteins. 2004 Nov 1;57(2):225-42. (PMID: 15340911)
Curr Top Med Chem. 2013;13(9):1127-38. (PMID: 23651486)
Cancer Res. 1997 Dec 1;57(23):5246-53. (PMID: 9393743)
ChemMedChem. 2014 Nov;9(11):2439-44. (PMID: 25146853)
Trends Biochem Sci. 2001 Jun;26(6):390-7. (PMID: 11406413)
J Chem Inf Model. 2012 Jun 25;52(6):1607-20. (PMID: 22646988)
Br J Pharmacol. 2011 Mar;162(6):1239-49. (PMID: 21091654)
Methods. 2015 Jan;71:26-37. (PMID: 25072167)
Brief Bioinform. 2009 Sep;10(5):579-91. (PMID: 19433475)
J Mol Graph Model. 2014 Sep;53:179-199. (PMID: 25173751)
Drug Metab Dispos. 1999 Feb;27(2):265-8. (PMID: 9929514)
Nat Rev Cancer. 2006 Jul;6(7):546-58. (PMID: 16794637)
Cell. 2004 Jan 23;116(2):205-19. (PMID: 14744432)
Hum Mutat. 2006 Jul;27(7):716. (PMID: 16786508)
Biomedicine (Taipei). 2015 Nov;5(4):19. (PMID: 26613930)
J Chem Phys. 2010 Nov 14;133(18):184110. (PMID: 21073216)
Chem Biol Interact. 2016 Apr 25;250:12-26. (PMID: 26954606)
J Comput Chem. 2005 Dec;26(16):1752-80. (PMID: 16211539)
J Comput Aided Mol Des. 2007 Dec;21(12):681-91. (PMID: 17899391)
Curr Opin Chem Biol. 2007 Oct;11(5):494-502. (PMID: 17936059)
Methods Mol Biol. 2014;1140:251-61. (PMID: 24590723)
J Med Chem. 2005 Feb 24;48(4):962-76. (PMID: 15715466)
Front Pharmacol. 2019 Apr 17;10:391. (PMID: 31057406)
J Theor Biol. 2013 Oct 7;334:87-100. (PMID: 23727278)
Methods. 2015 Jul 15;83:105-10. (PMID: 25920949)
Proteins. 2004 May 1;55(2):351-67. (PMID: 15048827)
تواريخ الأحداث: Date Created: 20210621 Latest Revision: 20220416
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8204324
DOI: 10.1021/acsptsci.0c00210
PMID: 34151203
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-9108
DOI:10.1021/acsptsci.0c00210