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Drug Discovery Today

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https://www.readbyqxmd.com/read/30213567/do-urocortins-have-a-role-in-treating-cardiovascular-disease
#1
REVIEW
Ekaterini Chatzaki, Nikoleta Kefala, Ioannis Drosos, Fani Lalidou, Stavroula Baritaki
Corticotropin-releasing factor (CRF) and the three homolog neuropeptides, urocortin (UCN) 1, 2 and 3, are the major neuroendocrine factors implicated in the response of the body to stress. Recent evidence suggests that UCNs have a significant role in the pathogenesis and management of cardiovascular disease, such as congestive heart failure, ischemic heart disease, and hypertension. These data led to the initiation of clinical trials testing a possible role of UCNs in the diagnosis and therapy of cardiovascular disease, with encouraging results...
September 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30213566/the-future-of-drug-development-the-paradigm-shift-towards-systems-therapeutics
#2
REVIEW
Meindert Danhof, Kevin Klein, Pieter Stolk, Murray Aitken, Hubert Leufkens
Progress in cell biology, genetics, molecular, and systems pharmacology is the driving force behind a current paradigm shift in drug research. This paradigm shift shapes new avenues for advanced treatments that are commonly referred to as 'systems therapeutics'. Systems therapeutics differ in many ways from current drugs because they target biological networks rather than single transduction pathways, and affect disease processes rather than physiological processes. Here, we examine how the paradigm shift towards systems therapeutics will change current scientific concepts of the interactions between drugs and diseases, the organization of research and development, as well as the clinical use and therapeutic evaluations of therapeutic interventions...
September 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30205170/3d-in-vitro-models-of-tumors-expressing-egfr-family-receptors-a-potent-tool-for-studying-receptor-biology-and-targeted-drug-development
#3
REVIEW
Evgeniya A Sokolova, Vladimir V Vodeneev, Sergey M Deyev, Irina V Balalaeva
Carcinomas overexpressing EGFR family receptors are of high clinical importance, because the receptors have prognostic value and are used as molecular targets for anticancer therapy. Insufficient drug efficacy necessitates further in-depth research of the receptor biology and improvement in preclinical stages of drug evaluation. Here, we review the currently used advanced 3D in vitro models of tumors, including tumor spheroids, models in natural and synthetic matrices, tumor organoids and microfluidic-based models, as a potent tool for studying EGFR biology and targeted drug development...
September 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30196006/a-well-tolerated-and-rapidly-acting-thiopurine-for-ibd
#4
Timothy H J Florin, John D Wright, Siddharth D Jambhrunkar, Michael G Henman, Amirali Popat
Thiopurine drugs continue to be a cornerstone of inflammatory bowel disease (IBD) treatment. Thiopurines are economical compared with many newer medical treatments for IBD, other chronic inflammatory diseases and leukaemia, although they are not without their shortcomings. These include a slow-onset therapeutic action and many adverse drug reactions. This feature article surveys published data, unpublished in vitro and in vivo experiments, as well as clinical experience, underpinning a rationale for bringing a novel thiopurine drug formulation to market...
September 7, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30176358/the-use-of-nanoparticles-as-biomaterials-in-dentistry
#5
REVIEW
Ranjeet A Bapat, Chaitanya P Joshi, Prachi Bapat, Tanay V Chaubal, Rohit Pandurangappa, Naveen Jnanendrappa, Bapi Gorain, Sukant Khurana, Prashant Kesharwani
Maintenance of oral health is a major challenge in dentistry. Different materials have been used to treat various dental diseases, although treatment success is limited by features of the biomaterials used. To overcome these limitations, materials incorporated with nanoparticles (NPs) can be used in dental applications including endodontics, periodontics, tissue engineering, oral surgery, and imaging. The unique properties of NPs, including their surface:volume ratio, antibacterial action, physical, mechanical, and biological characteristics, and unique particle size have rendered them effective vehicles for dental applications...
August 31, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30165198/cnidarian-peptide-neurotoxins-a-new-source-of-various-ion-channel-modulators-or-blockers-against-central-nervous-systems-disease
#6
REVIEW
Qiwen Liao, Yu Feng, Binrui Yang, Simon Ming-Yuen Lee
Cnidaria provide the largest source of bioactive peptides for new drug development. The venoms contain enzymes, potent pore-forming toxins and neurotoxins. The neurotoxins can immobilize predators rapidly when discharged via modifying sodium-channel-gating or blocking the potassium channel during the repolarization stage. Most cnidarian neurotoxins remain conserved under the strong influence of negative selection. Neuroactive peptides targeting the central nervous system through affinity with ion channels could provide insight leading to drug treatment of neurological diseases, which arise from ion channel dysfunctions...
August 27, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30125678/advancing-precision-medicine-with-personalized-drug-screening
#7
REVIEW
Kirill Gorshkov, Catherine Z Chen, Raisa E Marshall, Nino Mihatov, Yong Choi, Dac-Trung Nguyen, Noel Southall, Kevin G Chen, John K Park, Wei Zheng
Personalized drug screening (PDS) of approved drug libraries enables rapid development of specific small-molecule therapies for individual patients. With a multidisciplinary team including clinicians, researchers, ethicists, informaticians and regulatory professionals, patient treatment can be optimized with greater efficacy and fewer adverse effects by using PDS as an approach to find remedies. In addition, PDS has the potential to rapidly identify therapeutics for a patient suffering from a disease without an existing therapy...
August 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30121330/nanoengineered-delivery-systems-for-cancer-imaging-and-therapy-recent-advances-future-directions-and-patent-evaluation
#8
REVIEW
Ghazal Nabil, Ketki Bhise, Samaresh Sau, Mohamed Atef, Hossny A El-Banna, Arun K Iyer
Cancer is the second-highest cause of death worldwide. Several therapeutic approaches, such as conventional chemotherapy, antibodies and small-molecule inhibitors and nanotherapeutics, have been employed in battling cancer. Among them, nanotheranostics is an example of successful personalized medicine bearing the dual role of early diagnosis and therapy to cancer patients. In this review, we focus on various types of theranostic polymer and metal nanoparticles for their roles in cancer therapy and imaging concerning their limitations and future applications, such as dendritic cell cancer vaccination, gene delivery, T cell activation and immune modulation...
August 16, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30114523/biobanks-let-s-share-specimens
#9
EDITORIAL
Christopher J Ianelli
No abstract text is available yet for this article.
August 13, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30099123/selection-of-protein-conformations-for-structure-based-polypharmacology-studies
#10
REVIEW
Luca Pinzi, Fabiana Caporuscio, Giulio Rastelli
Several drugs exert their therapeutic effect through the modulation of multiple targets. Structure-based approaches hold great promise for identifying compounds with the desired polypharmacological profiles. These methods use knowledge of the protein binding sites to identify stereoelectronically complementary ligands. The selection of the most suitable protein conformations to be used in the design process is vital, especially for multitarget drug design in which the same ligand has to be accommodated in multiple binding pockets...
August 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30099124/new-leads-for-drug-repurposing-against-malaria
#11
REVIEW
Nila Madassary Pazhayam, Jyoti Chhibber-Goel, Amit Sharma
Malaria is threatening a resurgence because of drug resistance against frontline artemisinin-based combination therapies (ACTs). This necessitates the development of alternate routes for malaria treatment. Here, we present a refined focus on US Food and Drug Administration (FDA)-approved over-the-counter (OTC) drugs that could be repurposed. We analyzed growth inhibition data for Plasmodium falciparum and Plasmodium berghei in the context of 189 and 37 drugs (total of 226), respectively. Of these, our analyses revealed 18 currently used drugs that would be suitable for further development as potential antimalarials...
August 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30086405/effects-of-antidiabetic-drugs-on-nlrp3-inflammasome-activity-with-a-focus-on-diabetic-kidneys
#12
REVIEW
Habib Yaribeygi, Niki Katsiki, Alexandra E Butler, Amirhossein Sahebkar
Inflammatory responses have a pivotal role in the development of diabetic nephropathy (DN). The nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a newly recognized and potent inflammatory mediator that induces inflammatory responses in several disorders, including DN. The suppression of procytokine release and inflammatory response is integral to the prevention of complications arising from the inflammatory process. In this review, we discuss the role of the NLRP3 inflammasome in the pathogenesis of DN, focusing on its effects on interleukin (IL)-1β and IL-18...
August 4, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30086404/rna-mediated-therapies-in-myotonic-dystrophy
#13
REVIEW
Sarah J Overby, Estefanía Cerro-Herreros, Beatriz Llamusi, Ruben Artero
Myotonic dystrophy 1 (DM1) is a multisystemic neuromuscular disease caused by a dominantly inherited 'CTG' repeat expansion in the gene encoding DM Protein Kinase (DMPK). The repeats are transcribed into mRNA, which forms hairpins and binds with high affinity to the Muscleblind-like (MBNL) family of proteins, sequestering them from their normal function. The loss of function of MBNL proteins causes numerous downstream effects, primarily the appearance of nuclear foci, mis-splicing, and ultimately myotonia and other clinical symptoms...
August 4, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30086403/copies-of-nonbiological-complex-drugs-generic-hybrid-or-biosimilar
#14
REVIEW
Paolo Rocco, Umberto M Musazzi, Silvia Franzè, Paola Minghetti
The experience gained with biosimilars has made it clear that copies of complex drugs are more challenging to produce and put on the market than generics. In the case of so-called nonbiological complex drugs (NBCDs), the complexity can arise either from a complex active substance or by other factors, such as formulation or route of delivery. Regulatory policies in the USA and the EU for the marketing of NBCD copies are reviewed, using glatiramer acetate copies as a case study. In the USA, they are approved and marketed as generics (although needing additional data), and so they are interchangeable with the originator...
August 4, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30081096/turning-straw-into-gold-building-robustness-into-gene-signature-inference
#15
Wilson Wen Bin Goh, Limsoon Wong
Reproducible and generalizable gene signatures are essential for clinical deployment, but are hard to come by. The primary issue is insufficient mitigation of confounders: ensuring that hypotheses are appropriate, test statistics and null distributions are appropriate, and so on. To further improve robustness, additional good analytical practices (GAPs) are needed, namely: leveraging existing data and knowledge; careful and systematic evaluation of gene sets, even if they overlap with known sources of confounding; and rigorous testing of inferred signatures against as many published data sets as possible...
August 4, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30081095/mitochondrial-permeability-transition-pore-a-potential-drug-target-for-neurodegeneration
#16
REVIEW
Komal Kalani, Shi Fang Yan, Shirley ShiDu Yan
The mitochondrial permeability transition pore (mPTP) has been considered a key contributor to cell death, inducing the process in several major neurodegenerative diseases. To date, the molecular nature of the mPTP remains confounding but its significance is universally acknowledged. Several targets have been screened and inhibition of mPTP has emerged as an attractive field for researchers. Nowadays, in silico-directed studies help to explore new small molecules targeting the mPTP to improve their drug-like properties and bioactivity...
August 3, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30077779/ai-generated-in-silico-data-in-patent-applications
#17
EDITORIAL
Peter J Finnie
No abstract text is available yet for this article.
August 3, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30077780/temporary-removal-src-and-podoplanin-forge-a-path-to-destruction
#18
Harini Krishnan, W Todd Miller, Francisco J Blanco, Gary S Goldberg
Please note that Fig. 4 will be removed and will not figure in the final version of the article, since panels 4a and 4b represent unpublished results that have been included without appropriate permission. Panels 4c and 4d show reported results from Mayan-Santos, M.D. et al. Compositions and methods to treat inflammatory joint disease. Rowan University. PCT/US14/ 45229, currently inappropriately cited in the article." The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal...
August 2, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30077778/discovering-novel-valid-biomarkers-and-drugs-in-patient-centric-genomic-trials-the-new-epoch-of-precision-surgical-oncology
#19
REVIEW
Demosthenes E Ziogas, Ioannis D Kyrochristos, Dimitrios H Roukos
Despite standardization of multimodal treatment and approval of several targeted drugs for resectable, non-metastatic cancer (M0 patients), intrinsic and acquired resistance and relapse rates remain high, even in early-stage aggressive tumors. Genome analysis could overcome these unmet needs. Our comprehensive review underlines the controversy on stable or spatiotemporally evolving clones as well as promising yet inconclusive data on genome-based biomarkers and drug development. We propose clinicogenomic trials in M0 patients for the validation of intratumor heterogeneity (ITH), circulating genomic subclones (cGSs) and intra-patient genomic heterogeneity (IPGH) as biomarkers and simultaneous discovery of novel oncotargets...
August 2, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30071313/translational-in-vitro-research-integrating-3d-drug-discovery-and-development-processes-into-the-drug-development-pipeline
#20
Jens M Kelm, Madhu Lal-Nag, Gurusingham Sitta Sittampalam, Marc Ferrer
As we witness steady progress towards the development of robust, scalable, and reproducible 3D tissue models for preclinical drug testing, there is a need for systematic physiological and pharmacological validation and benchmarking. Ongoing and future studies should generate evidence as to whether 3D tissue models are more predictive, help reduce the risk of failure rate, and can be used for decision making in the drug discovery and development pipeline. Here, we discuss the importance of harmonizing the validation of these models based on throughput capacity and physiological complexity as a requirement to establish their true translational capacity...
July 30, 2018: Drug Discovery Today
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