Pharmacophore-based computational study on inhibitor of TMPRSS6 as hepcidin modulator in an iron overload of beta-thalassaemia

References

• Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology [Internet]. 2006;2006:29–35. doi:10.1182/asheducation-2006.1.29
   Google Scholar
• Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta - Mol Cell Res [Internet. 2012;1823:1434–1443. doi:10.1016/j.bbamcr.2012.01.014. Available from: https://www.sciencedirect.com/science/article/pii/S016748891200016X.
   PubMed Web of Science ®Google Scholar
• Saneela S, Iqbal R, Raza A, et al. Hepcidin: a key regulator of iron. J Pak Med Assoc. 2019;69:1170–1175.
   PubMed Web of Science ®Google Scholar
• Park CH, Valore E V, Waring AJ, et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276:7806–7810. doi:10.1074/jbc.M008922200
   PubMed Web of Science ®Google Scholar
• Liu J, Sun B, Yin H, et al. Hepcidin: a promising therapeutic target for iron disorders: a systematic review. Medicine (Baltimore). 2016;95:e3150. doi:10.1097/MD.0000000000003150
   PubMed Web of Science ®Google Scholar
• Ganz T. Hepcidin – A peptide hormone at the interface of innate immunity and iron metabolism. In: Shafer WM, editor. Antimicrob pept hum dis [Internet]. Berlin, Heidelberg: Springer Berlin Heidelberg; 2006. p. 183–198. doi:10.1007/3-540-29916-5_7
   Google Scholar
• Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi:10.1038/ng1777
   PubMed Web of Science ®Google Scholar
• Gomez-Puerto MC, Iyengar PV, de Vinuesa A G, et al. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol. 2019;247:9–20. doi:10.1002/path.5170
   PubMed Web of Science ®Google Scholar
• Canali S, Vecchi C, Garuti C, et al. The SMAD pathway is required for hepcidin response during endoplasmic reticulum stress. Endocrinology. 2016;157:3935–3945. doi:10.1210/en.2016-1258
   PubMed Web of Science ®Google Scholar
• Xiao X, Alfaro-Magallanes VM, Babitt JL. Bone morphogenic proteins in iron homeostasis. Bone. 2020;138:115495. doi:10.1016/j.bone.2020.115495
   PubMed Web of Science ®Google Scholar
• Pagani A, Nai A, Silvestri L, et al. Hepcidin and anemia: a tight relationship. Front Physiol [Internet]. 2019;10:1294. doi:10.3389/fphys.2019.01294
   PubMed Web of Science ®Google Scholar
• Ramsay AJ, Hooper JD, Folgueras AR, et al. Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematologica. 2009;94:840–849. doi:10.3324/haematol.2008.001867
   PubMed Web of Science ®Google Scholar
• Béliveau F, Tarkar A, Dion SP, et al. Discovery and development of TMPRSS6 inhibitors modulating hepcidin levels in human hepatocytes. Cell Chem Biol. 2019;26:1559–1572.e9. doi:10.1016/j.chembiol.2019.09.004
   PubMed Web of Science ®Google Scholar
• Silvestri L, Nai A, Dulja A, et al. Hepcidin and the BMP-SMAD pathway: an unexpected liaison. Vitam Horm. 2019;110:71–99. doi:10.1016/bs.vh.2019.01.004
   PubMed Web of Science ®Google Scholar
• Ramey G, Deschemin J-C, Durel B, et al. Hepcidin targets ferroportin for degradation in hepatocytes. Haematologica. 2010;95:501–504. doi:10.3324/haematol.2009.014399
   PubMed Web of Science ®Google Scholar
• Prentice S, Jallow AT, Sinjanka E, et al. Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates. Sci Rep. 2019;9:16596. doi:10.1038/s41598-019-52908-w
   PubMed Web of Science ®Google Scholar
• Folgueras AR, de Lara FM, Pendás AM, et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood [Internet]. 2008;112:2539–2545. doi:10.1182/blood-2008-04-149773. Available from: https://www.sciencedirect.com/science/article/pii/S0006497120598789.
   Google Scholar
• Riba M, Rausa M, Sorosina M, et al. A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6−/− mice. PLoS One [Internet]. 2013;8:1–14. doi:10.1371/journal.pone.0069694
   Web of Science ®Google Scholar
• Yu W, MacKerell ADJ. Computer-aided drug design methods. Methods Mol Biol. 2017;1520:85–106. doi:10.1007/978-1-4939-6634-9_5
   PubMedGoogle Scholar
• Muhammed MT, Aki-Yalcin E. Pharmacophore modeling in drug discovery: methodology and current status. J Turkish Chem Soc Sect A Chem. 2021;8:749–762. doi:10.18596/jotcsa.927426
   Google Scholar
• Silvestri L, Guillem F, Pagani A, et al. Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia. Blood [Internet]. 2009;113:5605–5608. doi:10.1182/blood-2008-12-195594
   Google Scholar
• Dassault Systèmes; San Diego, CA U. Dassault systèmes BIOVIA discovery studio visualizer v19.1.0.18287. 2019.
   Google Scholar
• Zardecki C, Dutta S, Goodsell DS, et al. RCSB protein Data Bank: a resource for chemical, biochemical, and structural explorations of large and small biomolecules. J Chem Educ. 2016;93:569–575. doi:10.1021/acs.jchemed.5b00404
   Web of Science ®Google Scholar
• Rao SN, Head MS, Kulkarni A, et al. Validation studies of the site-directed docking program LibDock. J Chem Inf Model. 2007;47:2159–2171. doi:10.1021/ci6004299
   PubMed Web of Science ®Google Scholar
• Wu G, Robertson DH, Brooks C3, et al. Detailed analysis of grid-based molecular docking: a case study of CDOCKER-A CHARMm-based MD docking algorithm. J Comput Chem. 2003;24:1549–1562. doi:10.1002/jcc.10306
   PubMed Web of Science ®Google Scholar
• Ashby J, Tennant RW. Chemical structure, salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP. Mutat Res Toxicol [Internet]. 1988;204:17–115. doi:10.1016/0165-1218(88)90114-0
   PubMed Web of Science ®Google Scholar
• Lemkul J. From proteins to perturbed hamiltonians: a suite of tutorials for the GROMACS-2018 molecular simulation package [Article v1.0]. Living J Comput Mol Sci. 2019;1:1–53. doi:10.33011/livecoms.1.1.5068
   Google Scholar
• Vanommeslaeghe K, Hatcher E, Acharya C, et al. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2010;31:671–690. doi:10.1002/jcc.21367
   PubMed Web of Science ®Google Scholar
• Irwin JJ, Shoichet BK. ZINC − a free database of commercially available compounds for virtual screening. J Chem Inf Model [Internet]. 2005;45:177–182. doi:10.1021/ci049714+
   PubMed Web of Science ®Google Scholar
• Gaulton A, Bellis LJ, Bento AP, et al. ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012;40:D1100–7. doi:10.1093/nar/gkr777
   PubMed Web of Science ®Google Scholar
• Gaulton A, Hersey A, Nowotka M, et al. The ChEMBL database in 2017. Nucleic Acids Res. 2017;45:D945–D954. doi:10.1093/nar/gkw1074
   PubMed Web of Science ®Google Scholar
• Kamaz Z, Jassani MJA-, Haruna U. Screening of common herbal medicines as promising direct inhibitors of sars-Cov-2 in Silico. Annu Res Rev Biol. 2020: 53–67. doi:10.9734/arrb/2020/v35i830260
   Google Scholar
• Prival MJ. Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals. Environ Mol Mutagen. 2001;37:55–69. doi:10.1002/1098-2280(2001)37:1<55::AID-EM1006>3.0.CO;2-5
   PubMed Web of Science ®Google Scholar
• Andersen HC. Molecular dynamics simulations at constant pressure and/or temperature. J Chem Phys. 1980;72:2384–2393. doi:10.1063/1.439486
   Web of Science ®Google Scholar
• Bekker H, Berendsen H, Dijkstra EJ, et al. Gromacs: a parallel computer for molecular dynamics simulations – ScienceOpen. Phys Comput. 1993;92:252–256.
   Google Scholar
• Abraham MJ, Murtola T, Schulz R, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX [Internet]. 2015;1–2:19–25. doi:10.1016/j.softx.2015.06.001. Available from: https://www.sciencedirect.com/science/article/pii/S2352711015000059.
   Google Scholar
• Nosé S. A molecular dynamics method for simulations in the canonical ensemble. Mol Phys. 1984;100:191–198. doi:10.1080/00268970110089108
   Google Scholar
• Vanommeslaeghe K, MacKerell ADJ. Automation of the CHARMM general force field (CGenFF) I: bond perception and atom typing. J Chem Inf Model [Internet]. 2012;52:3144–3154. doi:10.1021/ci300363c
   PubMed Web of Science ®Google Scholar
• Allen MP, Tildesley DJ. Computer simulation of liquids [Internet]. Oxford University Press; 2017. doi:10.1093/oso/9780198803195.001.0001
   Google Scholar
• Béliveau F, Tarkar A, Dion SP, et al. Discovery and development of TMPRSS6 inhibitors modulating hepcidin levels in human hepatocytes. Cell Chem Biol [Internet]. 2019;26:1559–1572.e9. doi:10.1016/j.chembiol.2019.09.004. Available from: https://www.sciencedirect.com/science/article/pii/S2451945619302788.
   PubMed Web of Science ®Google Scholar
• National Toxicology Program. NTP toxicology and carcinogenesis studies of chlorobenzene (CAS No. 108-90-7) in F344/N rats and B6C3F1 mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 1985;261:1–220.
   PubMedGoogle Scholar
• Gombar VK, Enslein K. Assessment of n-octanol/water partition coefficient: when is the assessment reliable? J Chem Inf Comput Sci. 1996;36:1127–1134. doi:10.1021/ci960028n
   PubMedGoogle Scholar
• Lee P. Role of matriptase-2 (TMPRSS6) in iron metabolism. Acta Haematol [Internet]. 2009;122:87–96. doi:10.1159/000243792
   PubMed Web of Science ®Google Scholar
• Sangkhae V, Nemeth E. Regulation of the iron homeostatic hormone hepcidin. Adv Nutr [Internet]. 2017;8:126–136. doi:10.3945/an.116.013961
   PubMed Web of Science ®Google Scholar
• Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122:78–86. doi:10.1159/000243791
   PubMed Web of Science ®Google Scholar
• Lakhal S, Schödel J, Townsend ARM, et al. Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis. J Biol Chem. 2011;286:4090–4097. doi:10.1074/jbc.M110.173096
   PubMed Web of Science ®Google Scholar
• Core AB, Canali S, Babitt JL. Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis. Front Pharmacol. 2014;5:1–9.
   PubMed Web of Science ®Google Scholar
• Xia Y, Babitt JL, Sidis Y, et al. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008;111:5195–5204. doi:10.1182/blood-2007-09-111567
   PubMed Web of Science ®Google Scholar
• Kowdley K V, Gochanour EM, Sundaram V, et al. Hepcidin signaling in health and disease: ironing out the details. Hepatol Commun [Internet]. 2021;5:723–735. doi:10.1002/hep4.1717
   PubMed Web of Science ®Google Scholar
• Casu C, Nemeth E, Rivella S. Hepcidin agonists as therapeutic tools. Blood J Am Soc Hematol. 2018;131:1790–1794.
   Google Scholar
• Ganz T, Nemeth E, Rivella S, et al. TMPRSS6 as a therapeutic target for disorders of erythropoiesis and iron homeostasis. Adv Ther [Internet]. 2023;40:1317–1333. doi:10.1007/s12325-022-02421-w
   PubMedGoogle Scholar
• Yadav PK, Singh AK. A review of iron overload in beta-thalassemia major, and a discussion on alternative potent iron chelation targets. Plasmatology. 2022;16. doi:10.1177/26348535221103560
   Google Scholar