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The Journal of Pediatrics Oct 2023
Topics: Infant, Newborn; Humans; Pharmacogenetics; Precision Medicine
PubMed: 37353149
DOI: 10.1016/j.jpeds.2023.113575 -
Medicina Clinica Feb 2024
Topics: Humans; Pharmacogenetics; Precision Medicine
PubMed: 38142210
DOI: 10.1016/j.medcli.2023.11.008 -
Journal of Medicinal Chemistry May 2024Earth is currently experiencing a mass extinction event. The flora and fauna of our planet are experiencing mass die-offs from a multitude of factors, with wildlife... (Review)
Review
Earth is currently experiencing a mass extinction event. The flora and fauna of our planet are experiencing mass die-offs from a multitude of factors, with wildlife disease emerging as one parameter where medicinal chemists are equipped to intervene. While contemporary medicinal chemistry focuses on human health, many traditional pharmaceutical companies have historic roots in human health, animal health, and plant health. This trifecta of health sciences perfectly maps to the current field of One Health, which recognizes that optimal health outcomes can only be achieved through the health of humans, plants, animals, and their shared environments. This Perspective imagines a world where state-of-the-art medicinal chemistry tactics are used to prevent the extinction of endangered species and points to preliminary work in the emerging area of conservation medicine.
Topics: Humans; Animals; Chemistry, Pharmaceutical; Endangered Species
PubMed: 38662285
DOI: 10.1021/acs.jmedchem.3c02334 -
Pharmacological Reviews Nov 2023The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This... (Review)
Review
The NR superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiologic processes. This review will summarize and discuss recent progress in NR biology and drug development derived from integrating various approaches, including biophysical techniques, structural studies, and translational investigation. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling. SIGNIFICANCE STATEMENT: Nuclear receptors (NRs) are ligand-regulated transcription factors that are critical regulators of myriad physiological processes. NRs serve as receptors for an array of drugs, and in this review, we provide an update on recent research into the roles of these drug targets.
Topics: Humans; Pharmacology, Clinical; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Carrier Proteins; Ligands
PubMed: 37586884
DOI: 10.1124/pharmrev.121.000436 -
Journal of Medicinal Chemistry Feb 2024This Perspective is the eighth in an annual series that summarizes successful fragment-to-lead (F2L) case studies published each year. A tabulated summary of relevant... (Review)
Review
This Perspective is the eighth in an annual series that summarizes successful fragment-to-lead (F2L) case studies published each year. A tabulated summary of relevant articles published in 2022 is provided, and features such as target class, screening methods, and ligand efficiency are discussed both for the 2022 examples and for the combined examples over the years 2015-2022. In addition, trends and new developments in the field are summarized. In 2022, 18 publications described successful fragment-to-lead studies, including the development of three clinical compounds (MTRX1719, MK-8189, and BI-823911).
Topics: Drug Discovery; Chemistry, Pharmaceutical; Publications; Ligands; Pyrimidines; Sulfur Compounds
PubMed: 38289623
DOI: 10.1021/acs.jmedchem.3c02070 -
Molecular Informatics Jan 2024In drug discovery, chemical language models (CLMs) originating from natural language processing offer new opportunities for molecular design. CLMs have been developed... (Review)
Review
In drug discovery, chemical language models (CLMs) originating from natural language processing offer new opportunities for molecular design. CLMs have been developed using recurrent neural network (RNN) or transformer architectures. For the predictive performance of RNN-based encoder-decoder frameworks and transformers, attention mechanisms play a central role. Among others, emerging application areas for CLMs include constrained generative modeling and the prediction of chemical reactions or drug-target interactions. Since CLMs are applicable to any compound or target data that can be presented in a sequential format and tokenized, mappings of different types of sequences can be learned. For example, active compounds can be predicted from protein sequence motifs. Novel off-the-beat-path applications can also be considered. For example, analogue series from medicinal chemistry can be perceived and represented as chemical sequences and extended with new compounds using CLMs. Herein, methodological features of CLMs and different applications are discussed.
Topics: Chemistry, Pharmaceutical; Drug Discovery; Electric Power Supplies; Models, Chemical; Natural Language Processing
PubMed: 38010610
DOI: 10.1002/minf.202300288 -
Psychological Medicine Dec 2023Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some... (Review)
Review
Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.
Topics: Humans; Pharmacogenetics; Psychiatry; Mental Disorders; Psychotropic Drugs; Algorithms
PubMed: 37772416
DOI: 10.1017/S0033291723002817 -
Journal of Clinical Psychopharmacology
Topics: Humans; Psychopharmacology; Artificial Intelligence
PubMed: 37683224
DOI: 10.1097/JCP.0000000000001752 -
Journal of Ethnopharmacology Dec 2023Asthma is often treated and prevented using the pharmacological properties of traditional medicinal plants. These healthcare systems are among the most well-known,... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Asthma is often treated and prevented using the pharmacological properties of traditional medicinal plants. These healthcare systems are among the most well-known, conveniently accessible, and economically priced in India and several other Asian countries. Traditional Indian Ayurvedic plants have the potential to be used as phyto-therapeutics, to create novel anti-asthmatic drugs, and as a cost-effective source of pharmaceuticals. Current conventional therapies have drawbacks, including serious side effects and expensive costs that interfere with treatment compliance and affect the patient's quality of life. The primary objective of the article is to comprehensively evaluate the advancement of research on the protective phytochemicals of traditional plants that target immune responses and signaling cascades in inflammatory experimental asthma models. The study would assist in paving the way for the creation of natural phytomedicines that are protective, anti-inflammatory, and immunomodulatory against asthma, which may then be used in individualized asthma therapy.
AIM OF THE STUDY
The study demonstrates the mechanisms of action of phytochemicals present in traditional medicinal plants, diminish pulmonary disorder in both in vivo and in vitro models of asthma.
MATERIALS AND METHODS
A comprehensive review of the literature on conventional plant-based asthma therapies was performed from 2006 to 2022. The study uses authoritative scientific sources such as PubMed, PubChem Compound, Wiley Online Library, Science Direct, Springer Link, and Google Scholar to collect information on potential phytochemicals and their mechanisms of action. World Flora Online (http://www.worldfloraonline.org) and Plants of the World Online (https://wcsp.science.kew.org) databases were used for the scientific names of medicinal plants.
RESULTS
The study outlines the phytochemical mechanisms of some traditional Ayurveda botanicals used to treat asthma. Active phytochemicals including curcumin, withaferin-A, piperine, glabridin, glycyrrhizin, 18β-glycyrrhetinic acid, trans-cinnamaldehyde, α-hederin, thymoquinone, eugenol, [6]-shogoal, and gingerol may treat asthma by controlling inflammation and airway remodeling. The study concluded that certain Ayurvedic plants' phytochemicals have the ability to reduce inflammation and modulate the immune system, that can effectively cure asthma.
CONCLUSION
Plants used in traditional Ayurvedic medicine have been utilized for millennia, advocating phyto-therapy as a treatment for a variety of illnesses. A theoretical foundation for the use of cutting-edge asthma treatments has been built with the growth of experimental research on traditional phytochemicals. In-depth phytochemical research for the treatment of asthma using Indian Traditional Ayurvedic herbs is compiled in the study. The approach for preventative therapeutics and cutting-edge alternatives to battle the molecular pathways in the pathophysiology of asthma are the key themes of the study. The phytochemical mechanism of action of traditional Ayurvedic herbs is explained to get the attention of the pharmaceutical industry so they can make future anti-asthma drugs for personalized asthma care in the community. The study develops strategies for customized phyto-therapeutics, concentrating on low-cost, side-effect-free approaches that employ bioactive phytochemicals from plants as the major source of effective anti-asthmatic therapy.
Topics: Humans; Plants, Medicinal; Phytotherapy; Quality of Life; Medicine, Traditional; Plant Extracts; Phytochemicals; Ethnopharmacology
PubMed: 37369335
DOI: 10.1016/j.jep.2023.116828 -
British Journal of Pharmacology Oct 2023The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format,...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Topics: Humans; Databases, Pharmaceutical; Ion Channels; Ligands; Receptors, G-Protein-Coupled; Databases, Factual; Pharmacology
PubMed: 38123150
DOI: 10.1111/bph.16178