| 1. |
- Apprato, Giulia, et al.
(författare)
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Exploring the chemical space of orally bioavailable PROTACs
- 2024
-
Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 29:4
-
Forskningsöversikt (refereegranskat)abstract
- A principal challenge in the discovery of proteolysis targeting chimeras (PROTACs) as oral medications is their bioavailability. To facilitate drug design, it is therefore essential to identify the chemical space where orally bioavailable PROTACs are more likely to be situated. To this aim, we extracted structure-bioavailability insights from published data using traditional 2D descriptors, thereby shedding light on their potential and limitations as drug design tools. Subsequently, we describe cuttingedge experimental, computational and hybrid design strategies based on 3D descriptors, which show promise for enhancing the probability of discovering PROTACs with high oral bioavailability.
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| 2. |
- Arvidsson, Per I., et al.
(författare)
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Open for collaboration : an academic platform for drug discovery and development at SciLifeLab
- 2016
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:10, s. 1690-1698
-
Forskningsöversikt (refereegranskat)abstract
- The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.
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| 3. |
- Bersani, Francesco S, et al.
(författare)
-
Telomerase activation as a possible mechanism of action for psychopharmacological interventions.
- 2015
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:11, s. 1305-1309
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Forskningsöversikt (refereegranskat)abstract
- Originally studied in relation to aging and cancer research, telomerase is now also investigated in relation to psychiatric disorders and treatments. Based on emerging clinical and preclinical data, we hypothesise that telomerase activation could represent a novel element mediating the mechanism of action of certain psychopharmacological interventions (e.g. antidepressants, lithium and antipsychotics). The modulation of intracellular Wnt/β-catenin or PI3K/Akt signalling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomerase activity. The potential of telomerase in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which the enzyme can mediate the therapeutic effect of such interventions.
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| 4. |
- Bignami, Francesca, et al.
(författare)
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Potential effects of increased openness in pharma : the original knowledge behind new drugs
- 2019
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832.
-
Tidskriftsartikel (refereegranskat)abstract
- This study seeks to determine potential changes in the degree of openness in pharmaceutical R&D by investigating where the knowledge behind new molecular entities (NMEs) comes from in terms of type of organization, geography and time. We find that the organizations granted NMEs increasingly rely on external knowledge sources but that these are increasingly shared among NME grantees. Universities are the most important indirect knowledge contributor and their relative importance has increased with time. NME grantees are increasingly relying on knowledge from different countries and the age of the knowledge sources confirms that recent NMEs are mostly follow-on drugs. This work provides evidence of the increasing openness of pharma to new knowledge sources as a means to improving the drug discovery and development process.
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| 5. |
- Bohlin, Lars, et al.
(författare)
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Podophyllotoxin derivatives : drug discovery and development
- 1996
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 1:8, s. 343-351
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Forskningsöversikt (refereegranskat)abstract
- The exploration and exploitation of podophyllin formulations provide an example of how a plant extract with established ethnomedical use, but also causing toxicity, can provide a basis for new drug discovery and development. Applications and potential applications include the treatment of venereal warts, psoriasis, rheumatoid arthritis, malaria and Alzheimer's disease. This review addresses the history and pharmacological action of these natural products and outlines the preclinical development and clinical trials of drugs in the pipeline and with marketing approval.
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| 6. |
- Borrebaeck, Carl, et al.
(författare)
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Progress in miniaturisation of proteon arrays - a step closer to high-density nanoarrays
- 2007
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 12:19-20, s. 813-819
-
Forskningsöversikt (refereegranskat)abstract
- Protein microarrays is a technology with great promise for high-throughput proteomics. Designing high-performance protein microarrays for global proteome analysis has, however, turned out to be challenging. To this end, major efforts are under way to design novel array formats capable of harboring the tremendous range of probes required to target complex proteomes composed of more than 10 000 analytes. By adopting nanotechnology, the first generation of miniaturized nanoarrays has recently emerged, which opens up new avenues for global proteome analysis and disease proteomics. This review describes the progress and key issues in designing miniaturized protein arrays.
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| 7. |
- Bosma, M
(författare)
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Lipid homeostasis in exercise
- 2014
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Ingår i: Drug discovery today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 19:7, s. 1019-1023
-
Tidskriftsartikel (refereegranskat)
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| 8. |
- Bostrom, PA
(författare)
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All organ exercise for metabolic health
- 2014
-
Ingår i: Drug discovery today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 19:7, s. 997-998
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
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| 9. |
- Bruhn, Jan G., et al.
(författare)
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Molecular Pharmacognosy : an explanatory model
- 1997
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 2:6, s. 243-246
-
Forskningsöversikt (refereegranskat)abstract
- Increased interest in the study of natural products as potential drugs and rapidly changing research strategies are driving us to reassess the role of pharmacognosy in the wider context of pharmaceutical research. The authors propose a new definition and an explanatory model of modern pharmacognosy that can be used as a theoretical foundation for future development of this classical branch of the life sciences.
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| 10. |
- Cheung, Herman H., et al.
(författare)
-
Monitor – Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:14, s. 621-622
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
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| 11. |
- Cheung, Herman H., et al.
(författare)
-
Monitor – Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:6, s. 287-290
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
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| 12. |
- Choudhury, Chinmayee, et al.
(författare)
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Structure-based drug repurposing : Traditional and advanced AI/ML-aided methods
- 2022
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 27:7, s. 1847-1861
-
Forskningsöversikt (refereegranskat)abstract
- The current global health emergency in the form of the Coronavirus 2019 (COVID-19) pandemic has highlighted the need for fast, accurate, and efficient drug discovery pipelines. Traditional drug discovery projects relying on in vitro high-throughput screening (HTS) involve large investments and sophisticated experimental set-ups, affordable only to big biopharmaceutical companies. In this scenario, application of efficient state-of-the-art computational methods and modern artificial intelligence (AI)-based algorithms for rapid screening of repurposable chemical space [approved drugs and natural products (NPs) with proven pharmacokinetic profiles] to identify the initial leads is a powerful option to save resources and time. Structure-based drug repurposing is a popular in silico repurposing approach. In this review, we discuss traditional and modern AI-based computational methods and tools applied at various stages for structure-based drug discovery (SBDD) pipelines. Additionally, we highlight the role of generative models in generating molecules with scaffolds from repurposable chemical space.
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| 13. |
- Colcloughl, Nicola, et al.
(författare)
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Building on the success of osimertinib : achieving CNS exposure in oncology drug discovery
- 2019
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 24:5, s. 1067-1073
-
Forskningsöversikt (refereegranskat)abstract
- Due to the blood-brain barrier (BBB) limiting the exposure of therapeutics to the central nervous system (CNS), patients with brain malignancies are challenging to treat, typically have poor prognoses, and represent a significant unmet medical need. Preclinical data report osimertinib to have significant BBB penetration and emerging clinical data demonstrate encouraging activity against CNS malignancies. Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing in BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.
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| 14. |
- Collin, Mattias, et al.
(författare)
-
Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:9, s. 420-422
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
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| 15. |
- Collin, Mattias, et al.
(författare)
-
Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:7, s. 338-340
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
|
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| 16. |
- Collin, Mattias, et al.
(författare)
-
Monitor – Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:24, s. 1082-1084
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
|
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| 17. |
- Collin, Mattias, et al.
(författare)
-
Monitor – biology
- 2005
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:15, s. 1073-1073
-
Tidskriftsartikel (refereegranskat)
|
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| 18. |
- Collin, Mattias, et al.
(författare)
-
Monitor – biology
- 2005
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:1, s. 75-77
-
Tidskriftsartikel (refereegranskat)
|
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| 19. |
- Collin, Mattias, et al.
(författare)
-
Monitor – biology
- 2005
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:7, s. 530-531
-
Tidskriftsartikel (refereegranskat)
|
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| 20. |
- Collin, Mattias, et al.
(författare)
-
Monitor – Biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:12, s. 539-541
-
Tidskriftsartikel (refereegranskat)abstract
- An insight into the latest developments in drug discovery through brief synopses of recent publications, summarizing the chemistry, pharmacological significance and biological relevance of new molecules.
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| 21. |
- Collin, Mattias, et al.
(författare)
-
Monitor – biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:19, s. 856-858
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
|
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| 22. |
- Collin, Mattias, et al.
(författare)
-
Monitor – biology
- 2005
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:17, s. 1201-1203
-
Tidskriftsartikel (refereegranskat)
|
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| 23. |
- Davis, Andrew M., et al.
(författare)
-
Limitations and lessons in the use of X-ray structural information in drug design
- 2008
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 13:19-20, s. 831-841
-
Forskningsöversikt (refereegranskat)abstract
- The use of X-ray crystal structure models continues to provide a strong stimulus to drug discovery, through the direct visualisation of ligand-receptor interactions. There is sometimes a limited appreciation of the uncertainties introduced during the process of deriving an atomic model from the experimentally observed electron density. Here, some of these uncertainties are highlighted with recent examples from the literature, together with snippets of advice for the medicinal chemist embarking on using X-ray crystal structure information in a drug discovery programme.
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| 24. |
- Di, Li, et al.
(författare)
-
Evidence-based approach to assess passive diffusion and carrier-mediated drug transport
- 2012
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 17:15-16, s. 905-912
-
Forskningsöversikt (refereegranskat)abstract
- Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty speculations are addressed to provide reliable guidance on choosing appropriate tools for drug design and optimization.
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| 25. |
|
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| 26. |
|
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| 27. |
|
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| 28. |
- Heath, Victoria, et al.
(författare)
-
Monitor – biology
- 2004
-
Ingår i: Drug Discovery Today. - 1878-5832. ; 9:15, s. 678-681
-
Tidskriftsartikel (refereegranskat)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
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| 29. |
- Hering, Jenny, et al.
(författare)
-
Structural basis for selective inhibition of antibacterial target MraY, a membrane-bound enzyme involved in peptidoglycan synthesis
- 2018
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 23:7, s. 1426-1435
-
Forskningsöversikt (refereegranskat)abstract
- The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase). We present a detailed comparison of interaction modes with the natural product inhibitors tunicamycin and muraymycin D2. Finally, we speculate on possible routes to design an antibacterial agent in the form of a potent and selective inhibitor against MraY.
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| 30. |
- Holgersson, Marcus, 1983, et al.
(författare)
-
Entrepreneurial patent management in pharmaceutical startups
- 2016
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:7, s. 1042-1045
-
Tidskriftsartikel (refereegranskat)abstract
- Startups fill an increasingly important role as innovators in the pharmaceutical industry, and patenting is typically central to their success. This article aims to explore patent management in pharmaceutical startups. The results show that startups need to deal with several challenges related to patenting and an ‘entrepreneurial’ approach to patent management is called for. Resource constraints, venture capital provision, exits and other conditions and events must be readily considered in the patent management process to build a successful pharmaceutical venture, something that could benefit the pharmaceutical industry as a whole.
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| 31. |
- Hosseinimehr, Seyed Jalal
(författare)
-
Flavonoids and genomic instability induced by ionizing radiation
- 2010
-
Ingår i: Drug Discovery Today. - 1359-6446 .- 1878-5832. ; 15:21-22, s. 907-918
-
Forskningsöversikt (refereegranskat)abstract
- DNA is the cellular target that has the most damage induced by ionizing radiation (IR). If genomic instability resulting from this DNA damage is not correctly repaired, it leads to mutation, cancer and cell death. Flavonoids are a family of natural products that affect oxidative stress and enhance genomic stability through DNA interaction. Although flavonoids exert protective effects against IR in normal cells, they enhance genotoxicity effects of this radiation in cancer cells, a beneficial effect that is of interest in the design of new anticancer pharmaceuticals. This review describes the molecular effects of IR on DNA structure and mechanisms by which flavonoids exert their effect on ionizing-radiation-induced genomic instability.
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| 32. |
- Hosseinimehr, Seyed Jalal, et al.
(författare)
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Liver uptake of radiolabeled targeting proteins and peptides : considerations for targeting peptide conjugate design
- 2012
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 17:21-22, s. 1224-1232
-
Tidskriftsartikel (refereegranskat)abstract
- Radionuclide imaging of molecular targets for cancer therapy is likely to be a powerful tool for patient stratification and response monitoring, allowing more personalized cancer treatment. Radiolabeled proteins and peptides are a promising class of imaging probes for visualization of molecular targets in vivo. However, hepatic uptake and hepatobiliary excretion of radioactivity can decrease imaging contrast, reducing the detection sensitivity of hepatic and extrahepatic abdominal metastases, respectively. In this article, we review factors that influence the hepatic uptake of radioactivity (e.g. the chemical nature of radiocatabolites and physicochemical properties of targeting peptides and linkers) to provide input for the rational design of peptide-based imaging probes.
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| 33. |
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| 34. |
- Jirstrand, Mats, 1968, et al.
(författare)
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Biochemical Modeling with Systems Biology Graphical Notation
- 2010
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 15:9-10, s. 365-370
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Tidskriftsartikel (refereegranskat)abstract
- The Systems Biology Graphical Notation (SBGN) is an emerging standard for graphical notation developed by an international systems biology community. Standardized graphical notation is crucial for efficient and accurate communication of biological knowledge between researchers with various backgrounds in the expanding field of systems biology. Here, we highlight SBGN from a practical point of view and describe how the user can build and simulate SBGN models from a simple drag-and-drop graphical user interface in PathwayLab.
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| 35. |
- Karlsson, Jan Olof G, et al.
(författare)
-
Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties.
- 2015
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:4, s. 411-421
-
Forskningsöversikt (refereegranskat)abstract
- Reactive oxygen species (ROS) and reactive nitrogen species (RNS) participate in pathological tissue damage. Mitochondrial manganese superoxide dismutase (MnSOD) normally keeps ROS and RNS in check. During development of mangafodipir (MnDPDP) as a magnetic resonance imaging (MRI) contrast agent, it was discovered that MnDPDP and its metabolite manganese pyridoxyl ethyldiamine (MnPLED) possessed SOD mimetic activity. MnDPDP has been tested as a chemotherapy adjunct in cancer patients and as an adjunct to percutaneous coronary intervention in patients with myocardial infarctions, with promising results. Whereas MRI contrast depends on release of Mn(2+), the SOD mimetic activity depends on Mn(2+) that remains bound to DPDP or PLED. Calmangafodipir [Ca4Mn(DPDP)5] is stabilized with respect to Mn(2+) and has superior therapeutic activity. Ca4Mn(DPDP)5 is presently being explored as a chemotherapy adjunct in a clinical multicenter Phase II study in patients with metastatic colorectal cancer.
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| 36. |
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| 37. |
- Kumar, Rajender, et al.
(författare)
-
Structural–functional analysis of drug target aspartate semialdehyde dehydrogenase
- 2024
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 29:3
-
Forskningsöversikt (refereegranskat)abstract
- Aspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibitors have two highly electronegative functional groups that interact with two key arginyl residues present in the active site of ASADHs. The structural information, active site binding modes, and key interactions between the enzyme and inhibitors serve as the basis for designing new and potent inhibitors against the ASADH family.
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| 38. |
- Lam, S., et al.
(författare)
-
A systems biology approach for studying neurodegenerative diseases
- 2020
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 25:7, s. 1146-1159
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative diseases (NDDs), such as Alzheimer's (AD) and Parkinson's (PD), are among the leading causes of lost years of healthy life and exert a great strain on public healthcare systems. Despite being first described more than a century ago, no effective cure exists for AD or PD. Although extensively characterised at the molecular level, traditional neurodegeneration research remains marred by narrow-sense approaches surrounding amyloid beta (A beta), tau, and alpha-synuclein (alpha-syn). A systems biology approach enables the integration of multi-omics data and informs discovery of biomarkers, drug targets, and treatment strategies. Here, we present a comprehensive timeline of high-throughput data collection, and associated biotechnological advancements and computational analysis related to AD and PD. We hereby propose that a philosophical change in the definitions of AD and PD is now needed.
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| 39. |
- Larhed, M, et al.
(författare)
-
Microwave-assisted high-speed chemistry : a new technique in drug discovery
- 2001
-
Ingår i: Drug Discovery Today. - Uppsala Univ, Uppsala Biomed Ctr, Dept Organ Pharmaceut Chem, SE-75123 Uppsala, Sweden.. - 1359-6446 .- 1878-5832. ; 6:8, s. 406-416
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Forskningsöversikt (refereegranskat)abstract
- In both lead identification and lead optimization processes there is an acute need for new organic small molecules. Traditional methods of organic synthesis are orders of magnitude too slow to satisfy the demand for these compounds. The fields of combinatorial and automated medicinal chemistry have been developed to meet the increasing requirement of new compounds for drug discovery; within these fields, speed is of the essence. The efficiency of microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven in several different fields of organic chemistry. We believe that the time saved by using focused microwaves is potentially important in traditional organic synthesis but could be of even greater importance in high-speed combinatorial and medicinal chemistry.
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| 40. |
- Ling, Charlotte, et al.
(författare)
-
Epigenetic adaptation to regular exercise in humans.
- 2014
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 19:7, s. 1015-1018
-
Forskningsöversikt (refereegranskat)abstract
- Regular exercise has numerous health benefits, for example, it reduces the risk of cardiovascular disease and cancer. It has also been shown that the risk of type 2 diabetes can be halved in high-risk groups through nonpharmacological lifestyle interventions involving exercise and diet. Nevertheless, the number of people living a sedentary life is dramatically increasing worldwide. Researchers have searched for molecular mechanisms explaining the health benefits of regular exercise for decades and it is well established that exercise alters the gene expression pattern in multiple tissues. However, until recently it was unknown that regular exercise can modify the genome-wide DNA methylation pattern in humans. This review will focus on recent progress in the field of regular exercise and epigenetics.
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| 41. |
- Los, Marek Jan, et al.
(författare)
-
Anticancer drugs of tomorrow : apoptotic pathways as targets for drug design
- 2003
-
Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 8:2, s. 67-77
-
Tidskriftsartikel (refereegranskat)abstract
- Apoptosis or programmed cell death is a set of ordered events that enables the selective removal of cells from tissue and is essential for homeostasis and proper function of multicellular organisms. Components of this signaling network, which include ligands, such as CD95, tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand, as well as downstream molecules, such as caspases, Bcl-2 family members, and inhibitor-of-apoptosis proteins, which trigger and regulate apoptosis, are crucial targets for conventional drug development and gene therapy of cancer and other diseases. Here, we focus on apoptotic pathways and propose new potential molecular targets that could prove effective in controlling cell death in the clinical setting.
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| 42. |
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| 43. |
- Mervin, Lewis H., et al.
(författare)
-
Uncertainty quantification in drug design
- 2021
-
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 26:2, s. 474-489
-
Forskningsöversikt (refereegranskat)abstract
- Machine learning and artificial intelligence are increasingly being applied to the drug-design process as a result of the development of novel algorithms, growing access, the falling cost of computation and the development of novel technologies for generating chemically and biologically relevant data. There has been recent progress in fields such as molecular de novo generation, synthetic route prediction and, to some extent, property predictions. Despite this, most research in these fields has focused on improving the accuracy of the technologies, rather than on quantifying the uncertainty in the predictions. Uncertainty quantification will become a key component in autonomous decision making and will be crucial for integrating machine learning and chemistry automation to create an autonomous design–make–test–analyse cycle. This review covers the empirical, frequentist and Bayesian approaches to uncertainty quantification, and outlines how they can be used for drug design. We also outline the impact of uncertainty quantification on decision making.
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| 44. |
- Molavipordanjani, Sajjad, et al.
(författare)
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Basic and practical concepts of radiopharmaceutical purification methods
- 2019
-
Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 24:1, s. 315-324
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Forskningsöversikt (refereegranskat)abstract
- The presence of radiochemical impurities in a radiopharmaceutical contributes to an unnecessary radiation burden for the patients or to an undesirable high radioactivity background, which reduces the imaging contrast or therapeutic efficacy. Therefore, if the radiolabeling process results in unsatisfactory radiochemical purity, a purification step is unavoidable. A successful purification process requires a profound knowledge about the radiopharmaceuticals of interest ranging from structural features to susceptibility to different conditions. Most radiopharmaceutical purification methods are based on solid phase extraction (SPE), high-performance liquid chromatography (HPLC), size exclusion chromatography (SEC), ion-exchange chromatography (IEC), and liquid-liquid extraction (LLE). Here, we discuss the basic and applied concepts of these purifications methods as well as their advantages and limitations.
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| 45. |
- Muliaditan, Morris, et al.
(författare)
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The implications of model-informed drug discovery and development for tuberculosis
- 2017
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Ingår i: Drug Discovery Today. - : ELSEVIER SCI LTD. - 1359-6446 .- 1878-5832. ; 22:3, s. 481-486
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Forskningsöversikt (refereegranskat)abstract
- Despite promising advances in the field and highly efficacious first-line treatment, an estimated 9.6 million people are still infected with tuberculosis (TB). Innovative methods are required to effectively transition the growing number of compounds into novel combination regimens. However, progression of compounds into patients occurs despite the lack of clear understanding of the pharmacokineticpharmacodynamic (PKPD) relationships. The PreDiCT-TB consortium was established in response to the existing gaps in TB drug development. The aim of the consortium is to develop new preclinical tools in concert with an in silico model-based approach, grounded in PKPD principles. Here, we highlight the potential impact of such an integrated framework on the various stages of TB drug development and on the dose rationale for drug combinations.
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| 46. |
- Murugan, N. A., et al.
(författare)
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Artificial intelligence in virtual screening : Models versus experiments
- 2022
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 27:7, s. 1913-1923
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Forskningsöversikt (refereegranskat)abstract
- A typical drug discovery project involves identifying active compounds with significant binding potential for selected disease-specific targets. Experimental high-throughput screening (HTS) is a traditional approach to drug discovery, but is expensive and time-consuming when dealing with huge chemical libraries with billions of compounds. The search space can be narrowed down with the use of reliable computational screening approaches. In this review, we focus on various machine-learning (ML) and deep-learning (DL)-based scoring functions developed for solving classification and ranking problems in drug discovery. We highlight studies in which ML and DL models were successfully deployed to identify lead compounds for which the experimental validations are available from bioassay studies.
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| 47. |
- Nielsen, Jens B, 1962, et al.
(författare)
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Improving the economics of NASH/NAFLD treatment through the use of systems biology
- 2017
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 22:10, s. 1532-1538
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD). We surveyed NASH therapies currently in development, and found a significant variety of targets and approaches. Evaluation and clinical testing of these targets is an expensive and time-consuming process. Systems biology approaches could enable the quantitative evaluation of the likely efficacy and safety of different targets. This motivated our review of recent systems biology studies that focus on the identification of targets and development of effective treatments for NASH. We discuss the potential broader use of genome-scale metabolic models and integrated networks in the validation of drug targets, which could facilitate more productive and efficient drug development decisions for the treatment of NASH.
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| 48. |
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| 49. |
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| 50. |
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