4,307 results match your criteria discovery sar

Molecular descriptor analysis of approved drugs using unsupervised learning for drug repurposing.

Comput Biol Med 2021 Sep 10;138:104856. Epub 2021 Sep 10.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; Advanced Computation and Data Sciences Division, CSIR - North East Institute of Science and Technology, Jorhat, Assam, 785 006, India. Electronic address:

Machine learning and data-driven approaches are currently being widely used in drug discovery and development due to their potential advantages in decision-making based on the data leveraged from existing sources. Applying these approaches to drug repurposing (DR) studies can identify new relationships between drug molecules, therapeutic targets and diseases that will eventually help in generating new insights for developing novel therapeutics. In the current study, a dataset of 1671 approved drugs is analyzed using a combined approach involving unsupervised Machine Learning (ML) techniques (Principal Component Analysis (PCA) followed by k-means clustering) and Structure-Activity Relationships (SAR) predictions for DR. Read More

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September 2021

Integrative Chemical Biology Approaches to Deciphering the Histone Code: A Problem-Driven Journey.

Acc Chem Res 2021 Sep 23. Epub 2021 Sep 23.

Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, 999077 China.

ConspectusThe hereditary blueprint of a eukaryotic cell is encoded in its genomic DNA that is tightly compacted into chromatin together with histone proteins. The basic repeating units of chromatin fibers are nucleosomes, in which approximately 1.7 turns of DNA wrap around a proteinaceous octamer consisting of two copies of histones H2A, H2B, H3, and H4. Read More

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September 2021

Treatment for Severe Lupus Nephritis: A Cost-Effectiveness Analysis in China.

Front Pharmacol 2021 6;12:678301. Epub 2021 Sep 6.

Division of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Lupus nephritis (LN) is the most common secondary glomerular diseases that will cause end-stage renal disease (ESRD) and renal-related death. The cost-effectiveness of various treatments for LN recommended by official guidelines has not been investigated in China. Our study is to evaluate clinical prognosis and cost-effectiveness of the current treatments for severe LN. Read More

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September 2021

Navigating into the Chemical Space of Monoamine Oxidase Inhibitors by Artificial Intelligence and Cheminformatics Approach.

ACS Omega 2021 Sep 1;6(36):23399-23411. Epub 2021 Sep 1.

Department of Pharmaceutical Chemistry and Analysis, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682041, India.

The monoamine oxidase (MAO) enzyme class is a prevalent target for many neurodegenerative and depressive disorders. Even though scrutinization of many promising drugs for the treatment of MAO inhibition has been carried out in recent times, a conclusive structural requirement for potent activity needs to be developed. Numerous approaches have been examined for the identification of structural features for potent MAO inhibitors (MAOIs) that mainly involve an array of computational studies, synthetic approaches, and biological evaluation. Read More

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September 2021

Public Attitudes and Factors of COVID-19 Testing Hesitancy in the United Kingdom and China: Comparative Infodemiology Study.

JMIR Infodemiology 2021 Jan-Dec;1(1):e26895. Epub 2021 Aug 27.

School of Public Health Fudan University Shanghai China.

Background: Massive community-wide testing has become the cornerstone of management strategies for the COVID-19 pandemic.

Objective: This study was a comparative analysis between the United Kingdom and China, which aimed to assess public attitudes and uptake regarding COVID-19 testing, with a focus on factors of COVID-19 testing hesitancy, including effectiveness, access, risk perception, and communication.

Methods: We collected and manually coded 3856 UK tweets and 9299 Chinese Sina Weibo posts mentioning COVID-19 testing from June 1 to July 15, 2020. Read More

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Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation.

Eur J Med Chem 2021 Sep 10;226:113823. Epub 2021 Sep 10.

Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Aberystwyth, SY23 3DA, United Kingdom. Electronic address:

Schistosomiasis is a neglected disease of poverty that is caused by infection with blood fluke species contained within the genus Schistosoma. For the last 40 years, control of schistosomiasis in endemic regions has predominantly been facilitated by administration of a single drug, praziquantel. Due to limitations in this mono-chemotherapeutic approach for sustaining schistosomiasis control into the future, alternative anti-schistosomal compounds are increasingly being sought by the drug discovery community. Read More

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September 2021

Urea transporter and its specific and nonspecific inhibitors: State of the art and pharmacological perspective.

Eur J Pharmacol 2021 Sep 16;911:174508. Epub 2021 Sep 16.

Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, MP, India; Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address:

Hypertension is a major concern for a wide array of patients. The traditional drugs are commonly referred as 'water pills' and these molecules have been successful in alleviating hypertension. However, this comes at the high expense of precious electrolytes in our body. Read More

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September 2021

Viral RNA and infectious influenza virus on mobile phones of influenza patients in Hong Kong and the United States.

J Infect Dis 2021 Sep 17. Epub 2021 Sep 17.

Maryland Institute for Applied Environmental Health, University of Maryland School of Public Health, College Park, Maryland, USA.

Mobile phones are among the most highly touched personal objects. As part of a broader study on the contribution of fomites to influenza transmission, between 2017-19, we swabbed mobile phones from 138 influenza patients in two locations. Influenza viral RNA detection rates were 23% (23/99) and 36% (14/39) in Hong Kong and Maryland, respectively. Read More

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September 2021

Dissociation of Connectivity for Syntactic Irregularity and Perceptual Ambiguity in Musical Chord Stimuli.

Front Neurosci 2021 30;15:693629. Epub 2021 Aug 30.

Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul, South Korea.

Musical syntax has been studied mainly in terms of "syntactic irregularity" in harmonic/melodic sequences. However, "perceptual ambiguity" referring to the uncertainty of judgment/classification of presented stimuli can in addition be involved in our musical stimuli using three different chord sequences. The present study addresses how "syntactic irregularity" and "perceptual ambiguity" on musical syntax are dissociated, in terms of effective connectivity between the bilateral inferior frontal gyrus (IFGs) and superior temporal gyrus (STGs) by linearized time-delayed mutual information (LTDMI). Read More

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Mangroves are an overlooked hotspot of insect diversity despite low plant diversity.

BMC Biol 2021 Sep 14;19(1):202. Epub 2021 Sep 14.

Center for Integrative Biodiversity Discovery, Leibniz Institute for Evolution and Biodiversity Science, Museum für Naturkunde, Invalidenstr. 43, Berlin, 10115, Germany.

Background: The world's fast disappearing mangrove forests have low plant diversity and are often assumed to also have a species-poor insect fauna. We here compare the tropical arthropod fauna across a freshwater swamp and six different forest types (rain-, swamp, dry-coastal, urban, freshwater swamp, mangroves) based on 140,000 barcoded specimens belonging to ca. 8500 species. Read More

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September 2021

Genetic screening reveals phospholipid metabolism as a key regulator of the biosynthesis of the redox-active lipid coenzyme Q.

Redox Biol 2021 Oct 8;46:102127. Epub 2021 Sep 8.

Heart Research Institute, The University of Sydney, Sydney, New South Wales, Australia; Victor Chang Cardiac Research Institute, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia. Electronic address:

Mitochondrial energy production and function rely on optimal concentrations of the essential redox-active lipid, coenzyme Q (CoQ). CoQ deficiency results in mitochondrial dysfunction associated with increased mitochondrial oxidative stress and a range of pathologies. What drives CoQ deficiency in many of these pathologies is unknown, just as there currently is no effective therapeutic strategy to overcome CoQ deficiency in humans. Read More

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October 2021

Scaffold Hopping to Imidazo[1,2-]pyrazin-8-one Positive Allosteric Modulators of Metabotropic Glutamate 2 Receptor.

ACS Omega 2021 Sep 25;6(35):22997-23006. Epub 2021 Aug 25.

Discovery Chemistry, Discovery Sciences, Janssen Research & Development, Division of Janssen-Cilag S.A., Jarama 75A, Toledo 45007, Spain.

Glutamate hyperfunction is implicated in multiple neurological and psychiatric diseases. Activation of the mGlu2 receptor results in reduced glutamate release and decreased excitability representing a promising novel therapeutic agent for the treatment of disorders such as epilepsy, schizophrenia, mood, anxiety, and other neuropsychiatric disorders. We have previously reported substantial efforts leading to potent and selective mGlu2 PAMs from different chemical series. Read More

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September 2021

A New Pipeline to Automatically Segment and Semi-Automatically Measure Bone Length on 3D Models Obtained by Computed Tomography.

Front Cell Dev Biol 2021 26;9:736574. Epub 2021 Aug 26.

Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.

The characterization of developmental phenotypes often relies on the accurate linear measurement of structures that are small and require laborious preparation. This is tedious and prone to errors, especially when repeated for the multiple replicates that are required for statistical analysis, or when multiple distinct structures have to be analyzed. To address this issue, we have developed a pipeline for characterization of long-bone length using X-ray microtomography (XMT) scans. Read More

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Discovery of a Potent Glutathione Peroxidase 4 Inhibitor as a Selective Ferroptosis Inducer.

J Med Chem 2021 Sep 10;64(18):13312-13326. Epub 2021 Sep 10.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.

Potent and selective ferroptosis regulators promote an intensive understanding of the regulation and mechanisms underlying ferroptosis, which is highly associated with various diseases. In this study, through a stepwise structure optimization, a potent and selective ferroptosis inducer was developed targeting to inhibit glutathione peroxidase 4 (GPX4), and the structure-activity relationship (SAR) of these compounds was uncovered. Compound exhibited outstanding GPX4 inhibitory activity with a percent inhibition up to 71. Read More

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September 2021

Fractionalized conductivity and emergent self-duality near topological phase transitions.

Nat Commun 2021 Sep 9;12(1):5347. Epub 2021 Sep 9.

Department of Physics and HKU-UCAS Joint Institute of Theoretical and Computational Physics, The University of Hong Kong, Hong Kong SAR, China.

The experimental discovery of the fractional Hall conductivity in two-dimensional electron gases revealed new types of quantum particles, called anyons, which are beyond bosons and fermions as they possess fractionalized exchange statistics. These anyons are usually studied deep inside an insulating topological phase. It is natural to ask whether such fractionalization can be detected more broadly, say near a phase transition from a conventional to a topological phase. Read More

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September 2021

SAR study of small molecule inhibitors of the programmed cell death-1/programmed cell death-ligand 1 interaction.

Chem Biol Drug Des 2021 Sep 8. Epub 2021 Sep 8.

Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc, Takatsuki, Osaka, Japan.

The development of small molecule inhibitors of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) has drawn research interest for the treatment of cancer. Recently, we reported the discovery of a novel dimeric core small molecule PD-1/PD-L1 inhibitor. In an effort to discover more potent inhibitors, we further explored the dimeric core scaffold. Read More

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September 2021

Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection.

Adv Sci (Weinh) 2021 Sep 8:e2102327. Epub 2021 Sep 8.

Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.

The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. Read More

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September 2021

Alzheimer's Disease and other Tauopathies: Exploring Efficacy of Medicinal Plant-Derived Compounds in Alleviating Tau-Mediated Neurodegeneration.

Curr Mol Pharmacol 2021 Sep 6. Epub 2021 Sep 6.

Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR. China.

Alzheimer's disease (AD), a major form of dementia, has been reported to affect more than 50 million people worldwide. It is characterized by the presence of amyloid-β (Aβ) plaques and hyperphosphorylated Tau-associated neurofibrillary tangles in the brain. Apart from AD, microtubule (MT)-associated protein Tau is also involved in other neurodegenerative diseases called tauopathies, including Pick's disease, frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration. Read More

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September 2021

Improving the performance stability of direct seawater electrolysis: from catalyst design to electrode engineering.

Nanoscale 2021 Sep 23;13(36):15177-15187. Epub 2021 Sep 23.

Department of Applied Biology and Chemical Technology and the State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.

Direct seawater electrolysis opens a new opportunity to lower the cost of hydrogen production from current water electrolysis technologies. To facilitate its commercialization, the challenges of long-term performance stability of electrochemical devices need to be first addressed and realized. This minireview summarised the common causes of performance decline during seawater electrolysis, from chemical reactions at the electrode surface to physical damage to the cell. Read More

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September 2021

Association between C-Maf-inducing protein gene rs2287112 polymorphism and schizophrenia.

PeerJ 2021 20;9:e11907. Epub 2021 Aug 20.

State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macao SAR, China.

Background: Schizophrenia is a severely multifactorial neuropsychiatric disorder, and the majority of cases are due to genetic variations. In this study, we evaluated the genetic association between the C-Maf-inducing protein ( gene and schizophrenia in the Han Chinese population.

Methods: In this case-control study, 761 schizophrenia patients and 775 healthy controls were recruited. Read More

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Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors.

Bioorg Med Chem Lett 2021 Sep 2;50:128352. Epub 2021 Sep 2.

EMD Serono Research and Development Institute, Inc., 45A Middlesex Turnpike, Billerica, MA 01821, USA.

Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. Read More

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September 2021

Preparation, biological & cheminformatics-based assessment of N,N-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials.

Bioorg Med Chem 2021 Aug 8;46:116348. Epub 2021 Aug 8.

Department of Biomedical Engineering, School of Engineering, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand. Electronic address:

Twenty eight new N,N-diphenylpyrimidine-2,4-diamines have been prepared in order to expand our understanding of the anti-malarial SAR of the scaffold. The aim of the study was to make structural modifications to improve the overall potency, selectivity and solubility of the series by varying the anilino groups attached to the 2- and 4-position. We evaluated the activity of the compounds against Plasmodium falciparum (Pf) 3D7, cytotoxicity against HepG2, % inhibition at a panel of 10 human kinases, solubility, permeability and lipophilicity, and human and rat in vitro clearance. Read More

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Synthetically-tailored and nature-derived dual COX-2/5-LOX inhibitors: Structural aspects and SAR.

Eur J Med Chem 2021 Aug 27;225:113804. Epub 2021 Aug 27.

Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, 500037, India. Electronic address:

Inflammation is a most complex pathological process that gives birth to different diseases. Different inflammatory mediators are released during an inflammation responsible for acute pain and chronic inflammatory diseases like cancer, asthma, rheumatoid arthritis, osteoarthritis, neurodegenerative diseases, metabolic and cardiovascular disorders. The arachidonic acid pathway, which results in the production of inflammatory mediators, provides several targets for anti-inflammatory intervention. Read More

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Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-Covalent -Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration.

J Med Chem 2021 Sep 1;64(18):13327-13355. Epub 2021 Sep 1.

D3-PharmaChemistry, Istituto Italiano di Tecnologia (IIT), 16163Genova, Italy.

Inhibition of intracellular -acylethanolamine-hydrolyzing acid amidase (NAAA) activity is a promising approach to manage the inflammatory response under disabling conditions. In fact, NAAA inhibition preserves endogenous palmitoylethanolamide (PEA) from degradation, thus increasing and prolonging its anti-inflammatory and analgesic efficacy at the inflamed site. In the present work, we report the identification of a potent, systemically available, novel class of NAAA inhibitors, featuring a pyrazole azabicyclo[3. Read More

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September 2021

Complete Genetic Analysis of Plasmids Carried by Two Nonclonal - and -Bearing Escherichia coli Strains: Insight into Plasmid Transmission among Foodborne Bacteria.

Microbiol Spectr 2021 Sep 1:e0021721. Epub 2021 Sep 1.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR.

Our objective was to characterize the genetic features of plasmids harbored by two genetically related, MCR-1 and NDM-5-producing Escherichia coli strains recovered from a chicken meat sample. The genetic profiles of all plasmids harbored by the two test strains, namely, 1106 and 1107, were determined by whole-genome sequencing, S1-pulsed-field gel electrophoresis (PFGE), Southern hybridization, and bioinformatics analysis. The transferability of plasmids harbored by the two strains was assessed by filter mating assay. Read More

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September 2021

Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies.

Arch Pharm (Weinheim) 2021 Aug 31:e2100258. Epub 2021 Aug 31.

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Nasr City, Egypt.

Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. Read More

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AZD0284, a Potent, Selective, and Orally Bioavailable Inverse Agonist of Retinoic Acid Receptor-Related Orphan Receptor C2.

J Med Chem 2021 Sep 31;64(18):13807-13829. Epub 2021 Aug 31.

Pharmaron Beijing Co., Ltd., Taihe Road BDA, Beijing 100176, P. R. China.

Inverse agonists of the nuclear receptor RORC2 have been widely pursued as a potential treatment for a variety of autoimmune diseases. We have discovered a novel series of isoindoline-based inverse agonists of the nuclear receptor RORC2, derived from our recently disclosed RORC2 inverse agonist . Extensive structure-activity relationship (SAR) studies resulted in AZD0284 (), which combined potent inhibition of IL-17A secretion from primary human T17 cells with excellent metabolic stability and good PK in preclinical species. Read More

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September 2021

An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.

Handb Exp Pharmacol 2021 Sep 1. Epub 2021 Sep 1.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Since the discovery of the proto-oncogene Wnt1 (Int1) in 1982, WNT signaling has been identified as one of the most important pathways that regulates a wide range of fundamental developmental and physiological processes in multicellular organisms. The canonical WNT signaling pathway depends on the stabilization and translocation of β-catenin and plays important roles in development and homeostasis. The WNT/planar cell polarity (WNT/PCP) signaling, also known as one of the β-catenin-independent WNT pathways, conveys directional information to coordinate polarized cell behaviors. Read More

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September 2021

Positive allosteric modulators (PAMs) of the group II metabotropic glutamate receptors: Design, synthesis, and evaluation as ex-vivo tool compounds.

Bioorg Med Chem Lett 2021 Aug 27;50:128342. Epub 2021 Aug 27.

Warren Center for Neuroscience Drug Discovery at Vanderbilt University, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address:

This letter describes synthesis and evaluation of two series of dual mGlu/mGlu positive allosteric modulators with moderate mGlu potency and robust mGlu potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu-mediated signaling in central neurons by co-application of a selective mGlu NAM to isolate mGlu-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca signaling in PFC pyramidal cells with either the dual mGlu/mGlu PAM 16e or 23d demonstrated effects mediated selectively via mGlu. Read More

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Facile conversion of molecularly complex (hetero)aryl carboxylic acids into alkynes for accelerated SAR exploration.

Chemistry 2021 Aug 30. Epub 2021 Aug 30.

Janssen Pharmaceutica NV, Discovery Process Research, BELGIUM.

1,2,3-Triazoles are well-established bioisosteres for amides, often installed as a result of structure-activity-relationship (SAR) exploration. A straightforward approach to assess the effect of the replacement of an amide by a triazole would start from the carboxylic acid and the amine used for the formation of a given amide and convert them into the corresponding alkyne and azide for cyclization via copper-catalyzed alkyne-azide cycloaddition (CuAAC). Herein, we report a functional-group-tolerant and operationally simple decarbonylative alkynylation reaction allowing the conversion of complex (hetero)aryl carboxylic acids into alkynes. Read More

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