PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
Tytuł artykułu

Polypharmacology – a challenge for current drug design approaches

Treść / Zawartość
Identyfikatory
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Drug design process faces many challenges, and the most important ones are connected with side effects. Finding compounds that possess affinity towards target of interest is relatively simple; however, an approach one disease-one target is now making space for the search of polypharmacological ligands, where activity towards several proteins is considered at one time. Such proteins are not always the target ones, but very often such panels include also anti-targets, interaction with which is not desired, due to the side effects that may occur upon such contact. In the study, we examined ligands of four G protein-coupled receptors, forming antipsychotic profile: dopamine receptor D2, serotonin receptors 5-HT2A, 5-HT2C (anti-target), and 5-HT6. Number of ligands belonging to particular activity groups, as well as the selected compound structures are examined in detail. Also compound similarity between sets of different activity groups is analysed, giving a picture of difficulty of constructing molecular modeling methodologies that can help in the search of compounds with desired activity profile.
Rocznik
Strony
19--23
Opis fizyczny
Bibliogr. 21 poz., rys., tab.
Twórcy
  • Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31–343 Kraków, Poland
  • Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30–688 Kraków, Poland
  • Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31–343 Kraków, Poland
Bibliografia
  • 1. Hughes J.P., Rees S.S., Kalindjian S.B., Philpott K.L.: Principles of Early Drug Discovery. British Journal of Pharmacology. 2011; 162: 1239–1249.
  • 2. Trist D.G.: Scientific Process, Pharmacology and Drug Discovery. Current Opinion in Pharmacology. 2011; 11: 528–533.
  • 3. Wang J., Li Z., Qiu C., Wang D., Cui Q.: The Relationship between Rational Drug Design and Drug Side Effects. Briefings in Bioinformatics. 2012; 13: 377–382.
  • 4. Dessalew N., Mikre W.: On the Paradigm Shift towards Multitarget Selective Drug Design. Current Computer-Aided Drug Design. 2008; 4: 76–90.
  • 5. Katritch V., Cherezov V., Stevens R.C.: Structure-Function of the G Protein-Coupled Receptor Superfamily. Annual Review of Pharmacology and Toxicology. 2013; 53: 531–556.
  • 6. Nichols D.E., Nichols C.D.: Serotonin Receptors. Chemical Reviews. 2008; 108: 1614–1641.
  • 7. Berger M., Gray J.A., Roth B.L.: The Expanded Biology of Serotonin. Annual Review of Medicine. 2009; 60: 355–366.
  • 8. Kessler R.C., Aguilar-Gaxiola S., Alonso J., Chatterji S., Lee S., Ormel J., Ustün T.B., Wang P.S.: The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiology and Psychiatric Sciences. 2011; 18: 23–33.
  • 9. Kato M., Serretti A.: Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular Psychiatry. 2010; 15: 473–500.
  • 10. Gaulton A., Bellis L.J., Bento A.P., Chambers J., Davies M., Hersey A., Light Y., McGlinchey S., Michalovich D., Al-Lazikani B., Overington J.P.: ChEMBL: A Large-Scale Bioactivity Database for Drug Discovery. Nucleic Acids Research. 2012; 40: D1100–D1107.
  • 11. Warszycki D., Mordalski S., Kristiansen K., Kafel R., Sylte I., Chilmonczyk Z., Bojarski A.J.: A Linear Combination of Pharmacophore Hypotheses as a New Tool in Search of New Active Compounds - An Application for 5-HT1A Receptor Ligands. PLoS One. 2013; 8: e84510.
  • 12. InstantJChem Version 15.3.30.0, 2015, Licensed by ChemAxon; www.chemaxon.com (accessed September 203 2019).
  • 13. http://bioinformatics.psb.ugent.be/publications/
  • 14. Wang S., Che T., Levit A., Shoichet B.K., Wacker D., Roth B.L.. Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature. 2018; 555: 269–273.
  • 15. Kimura T.K., Asada H., Inoue A., Kadji F.M.N., Im D., Mori C., Arakawa T., Hirata K., Nomura N., Aoki J., Iwata S., Shimamura T.. Structures of the 5-HT2A receptor in complex with the antipsychotics risperidone and zotepin. Nature Structural & Molecular Biology. 2019; 26: 121–128.
  • 16. Schrödinger Release 2019-3: LigPrep, Schrödinger, LLC, New York, NY, 2019
  • 17. Schrödinger Release 2019-3: Glide, Schrödinger, LLC, New York, NY, 2019
  • 18. Pándy-Szekeres G., Munk C., Tsonkov T.M., Mordalski S., Harpsøe K., Hauser A.S., Bojarski A.J., Gloriam D.E.: GPCRdb in 2018: adding GPCR structure models and ligands. Nucleic Acids Research. 2017; D1: D440–D446.
  • 19. The PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC.
  • 20. Rogers D., Hahn M.: Extended-Connectivity Fingerprints: Journal of Chemical Information and Modeling. 2010; 50: 742–754.
  • 21. Bajusz D., Racz A., Heberger K.: Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations? Journal of Cheminformatics. 2015; 7: 20.
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-405a818a-b5ca-47a7-86e3-af5615a77418
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.