Fragment based drug design
-
Rahul Ashok Sachdeo
Abstract
Rational approaches towards drug development have emerged as one of the most promising ways among the tedious conventional procedures with the aim of redefining the drug discovery process. The need of current medical system is demanding a much precise, faster and reliable approaches in parallel to faster growing technology for development of drugs with more intrinsic action and fewer side effects. Systematic and well-defined diagnostic studies have revealed the specific causes of disease and related targets for drug development. Designing a drug as per the specific target, studying it in-silico prior to its development has been proved as an added benefit to the studies. Many approaches like structure based drug design, fragment based drug design and ligand based drug design are been in practice for the drug discovery and development with the similar fundamental theory. Fragment based drug design utilizes a library of fragments designed specifically for the concerned target and these fragments are studied further before screening with virtual methods as well as with biophysical methods. The process follows a well-defined pathway which moulds a fragment into a perfect drug candidate. In this chapter we have tried to cover all the basic aspects of fragment based drug design and related technologies.
-
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
-
Research funding: None declared.
-
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Kirsch, P, Hartman, AM, Hirsch, AKH, Empting, M. Concepts and core principles of fragment-based drug design. Molecules 2019;24:1–22. https://doi.org/10.3390/molecules24234309.Suche in Google Scholar PubMed PubMed Central
2. St. Denis JD, Hall, RJ, Murray, CW, Heightman, TD, Rees, DC. Fragment-based drug discovery: opportunities for organic synthesis. RSC Med Chem 2021;12:321. https://doi.org/10.1039/D0MD00375A.Suche in Google Scholar
3. Hubbard, RE. The role of fragment-based discovery in lead finding. Hoboken, NJ: Wiley-VCH Verlag GmbH & Co. KGaA; 2016:1–36 pp.10.1002/9783527683604.ch01Suche in Google Scholar
4. Murray, CW, Rees, DC. The rise of fragment-based drug discovery. Nat Chem 2009;1:187–92. https://doi.org/10.1038/nchem.217.Suche in Google Scholar PubMed
5. Murray, CW, Verdonk, ML, Rees, DC. Experiences in fragment-based drug discovery. Trends Pharmacol Sci 2012;33:224–32. https://doi.org/10.1016/j.tips.2012.02.006.Suche in Google Scholar PubMed
6. Doak, BC, Norton, RS, Scanlon, MJ. The ways and means of fragment-based drug design. Pharmacol Therapeut 2016;167:28–37. https://doi.org/10.1016/j.pharmthera.2016.07.003.Suche in Google Scholar PubMed
7. FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC; 2021. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sotorasib-kras-g12c-mutated-nsclc [Accessed 4 Aug 2021].Suche in Google Scholar
8. Fragments in the clinic: 2020 edition; 2020. Available from: http://practicalfragments.blogspot.com/2020/03/fragments-in-clinic-2020-edition.html [Accessed 4 Aug 2021].Suche in Google Scholar
9. Sheng, C, Zhang, W. Fragment informatics and computational fragment-based drug design: an overview and update. Med Res Rev 2013;33:554–98. https://doi.org/10.1002/med.21255.Suche in Google Scholar PubMed
10. Hoffer, L, Renaud, J-P, Horvath, D. Fragment-based drug design: computational and experimental state of the art. Comb Chem High Throughput Screen 2011;14:500–20. https://doi.org/10.2174/138620711795767884.Suche in Google Scholar PubMed
11. Jacquemard, C, Kellenberger, E. A bright future for fragment-based drug discovery: what does it hold? Vol. 14, Expert opinion on drug discovery. London: Taylor and Francis Ltd; 2019:413–6 pp.10.1080/17460441.2019.1583643Suche in Google Scholar PubMed
12. Konteatis, Z. What makes a good fragment in fragment-based drug discovery? Expert. Opin. Drug. Discov. 2021;16:723–6.10.1080/17460441.2021.1905629Suche in Google Scholar PubMed
13. Erlanson, DA, Fesik, SW, Hubbard, RE, Jahnke, W, Jhoti, H. Twenty years on: the impact of fragments on drug discovery. Nat Rev Drug Discov 2016:15;605–19.10.1038/nrd.2016.109Suche in Google Scholar PubMed
14. Li, Qingxin. Application of fragment-based drug discovery to versatile targets. Vol. 7, Frontiers in molecular biosciences. Switzerland: Frontier; 2020, 7:1–13 pp.10.3389/fmolb.2020.00180Suche in Google Scholar PubMed PubMed Central
15. Price, AJ, Howard, S, Cons, BD. Fragment-based drug discovery and its application to challenging drug targets. Vol. 16, Essays in biochemistry. Portland Press Ltd; 2017:475–84 pp.10.1042/EBC20170029Suche in Google Scholar PubMed
16. Kumar, A, Voet, A, Zhang, KYJ. Fragment based drug design: from experimental to computational approaches. Curr Med Chem 2012;19:5128–47. https://doi.org/10.2174/092986712803530467.Suche in Google Scholar PubMed
17. Bartoschik, T, Maschberger, M, Feoli, A, Andre, T, Baaske, P, Duhr, S, et al.. Microscale thermophoresis in drug discovery. Appl Biophy Drug Discov 2017;1:73–92.10.1002/9781119099512.ch5Suche in Google Scholar
18. Ohlson, S, Duong-Thi, MD. Fragment-based drug discovery: lessons and outlook. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2016, vol 1, 173–91 pp.10.1002/9783527683604.ch08Suche in Google Scholar
19. Erlanson, DA, McDowell, RS, O’Brien, T. Fragment-based drug discovery. J Med Chem 2004;47:3463–82. https://doi.org/10.1021/jm040031v.Suche in Google Scholar PubMed
20. Pedro, L, Quinn, RJ. Native mass spectrometry in fragment-based drug discovery. Molecules 2016;21:1–16. https://doi.org/10.3390/molecules21080984.Suche in Google Scholar PubMed PubMed Central
21. Jayanthi, S. The versatility of isothermal titration calorimetry in modern biology. J Anal Bioanal Tech 2015;06:1–3. https://doi.org/10.4172/2155-9872.1000e121.Suche in Google Scholar
22. Bian, Y, Xie, XQ (Sean). Computational fragment-based drug design: current trends, strategies, and applications. AAPS J 2018;20:1–11. https://doi.org/10.1208/s12248-018-0216-7.Suche in Google Scholar PubMed PubMed Central
23. Lamoree, B, Hubbard, RE. Current perspectives in fragment-based lead discovery (FBLD). Essays Biochem 2017;61:453–64.10.1042/EBC20170028Suche in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- Magnetic characterization of magnetoactive elastomers containing magnetic hard particles using first-order reversal curve analysis
- Microscopic understanding of particle-matrix interaction in magnetic hybrid materials by element-specific spectroscopy
- Biodeinking: an eco-friendly alternative for chemicals based recycled fiber processing
- Bio-based polyurethane aqueous dispersions
- Cellulose-based polymers
- Biodegradable shape-memory polymers and composites
- Natural substances in cancer—do they work?
- Personalized and targeted therapies
- Identification of potential histone deacetylase inhibitory biflavonoids from Garcinia kola (Guttiferae) using in silico protein-ligand interaction
- Chemical computational approaches for optimization of effective surfactants in enhanced oil recovery
- Social media and learning in an era of coronavirus among chemistry students in tertiary institutions in Rivers State
- Techniques for the detection and quantification of emerging contaminants
- Occurrence, fate, and toxicity of emerging contaminants in a diverse ecosystem
- Updates on the versatile quinoline heterocycles as anticancer agents
- Trends in microbial degradation and bioremediation of emerging contaminants
- Power to the city: Assessing the rooftop solar photovoltaic potential in multiple cities of Ecuador
- Phytoremediation as an effective tool to handle emerging contaminants
- Recent advances and prospects for industrial waste management and product recovery for environmental appliances: a review
- Integrating multi-objective superstructure optimization and multi-criteria assessment: a novel methodology for sustainable process design
- A conversation on the quartic equation of the secular determinant of methylenecyclopropene
- Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules
- An overview of in silico methods used in the design of VEGFR-2 inhibitors as anticancer agents
- Fragment based drug design
- Advances in heterocycles as DNA intercalating cancer drugs
- Systems biology–the transformative approach to integrate sciences across disciplines
- Pharmaceutical interest of in-silico approaches
- Membrane technologies for sports supplementation
- Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents
- Membrane applications in the food industry
- Membrane techniques in the production of beverages
- Statistical methods for in silico tools used for risk assessment and toxicology
- Dicarbonyl compounds in the synthesis of heterocycles under green conditions
- Green synthesis of triazolo-nucleoside conjugates via azide–alkyne C–N bond formation
- Anaerobic digestion fundamentals, challenges, and technological advances
- Survival is the driver for adaptation: safety engineering changed the future, security engineering prevented disasters and transition engineering navigates the pathway to the climate-safe future
Artikel in diesem Heft
- Frontmatter
- Reviews
- Magnetic characterization of magnetoactive elastomers containing magnetic hard particles using first-order reversal curve analysis
- Microscopic understanding of particle-matrix interaction in magnetic hybrid materials by element-specific spectroscopy
- Biodeinking: an eco-friendly alternative for chemicals based recycled fiber processing
- Bio-based polyurethane aqueous dispersions
- Cellulose-based polymers
- Biodegradable shape-memory polymers and composites
- Natural substances in cancer—do they work?
- Personalized and targeted therapies
- Identification of potential histone deacetylase inhibitory biflavonoids from Garcinia kola (Guttiferae) using in silico protein-ligand interaction
- Chemical computational approaches for optimization of effective surfactants in enhanced oil recovery
- Social media and learning in an era of coronavirus among chemistry students in tertiary institutions in Rivers State
- Techniques for the detection and quantification of emerging contaminants
- Occurrence, fate, and toxicity of emerging contaminants in a diverse ecosystem
- Updates on the versatile quinoline heterocycles as anticancer agents
- Trends in microbial degradation and bioremediation of emerging contaminants
- Power to the city: Assessing the rooftop solar photovoltaic potential in multiple cities of Ecuador
- Phytoremediation as an effective tool to handle emerging contaminants
- Recent advances and prospects for industrial waste management and product recovery for environmental appliances: a review
- Integrating multi-objective superstructure optimization and multi-criteria assessment: a novel methodology for sustainable process design
- A conversation on the quartic equation of the secular determinant of methylenecyclopropene
- Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules
- An overview of in silico methods used in the design of VEGFR-2 inhibitors as anticancer agents
- Fragment based drug design
- Advances in heterocycles as DNA intercalating cancer drugs
- Systems biology–the transformative approach to integrate sciences across disciplines
- Pharmaceutical interest of in-silico approaches
- Membrane technologies for sports supplementation
- Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents
- Membrane applications in the food industry
- Membrane techniques in the production of beverages
- Statistical methods for in silico tools used for risk assessment and toxicology
- Dicarbonyl compounds in the synthesis of heterocycles under green conditions
- Green synthesis of triazolo-nucleoside conjugates via azide–alkyne C–N bond formation
- Anaerobic digestion fundamentals, challenges, and technological advances
- Survival is the driver for adaptation: safety engineering changed the future, security engineering prevented disasters and transition engineering navigates the pathway to the climate-safe future
