scholarly journals Polypharmacologicalin SilicoBioactivity Profiling and Experimental Validation Uncovers Sedative-Hypnotic Effects of Approved and Experimental Drugs in Rat

2017 ◽  
Vol 12 (6) ◽  
pp. 1593-1602 ◽  
Author(s):  
Georgios Drakakis ◽  
Keith A. Wafford ◽  
Suzanne C. Brewerton ◽  
Michael J. Bodkin ◽  
David A. Evans ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Experimental Drugs

scholarly journals Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2

2020 ◽  
Author(s):  
Tesia Bobrowski ◽  
Vinicius Alves ◽  
Cleber C. Melo-Filho ◽  
Daniel Korn ◽  
Scott S. Auerbach ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Similarity Search ◽  
Experimental Validation ◽  
Computational Models ◽  
Qsar Modeling ◽  
Human Coronavirus ◽  
Sequence Identity ◽  
Experimental Drugs ◽  
Investigational Drugs ◽  
Qsar Models

The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation.<br>

scholarly journals Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2

2020 ◽  
Author(s):  
Tesia Bobrowski ◽  
Vinicius Alves ◽  
Cleber C. Melo-Filho ◽  
Daniel Korn ◽  
Scott S. Auerbach ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Similarity Search ◽  
Experimental Validation ◽  
Computational Models ◽  
Qsar Modeling ◽  
Human Coronavirus ◽  
Sequence Identity ◽  
Experimental Drugs ◽  
Investigational Drugs ◽  
Qsar Models

The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation.<br>

Experimental validation of the predicted TGR5 binding mode model

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
L Spomer ◽  
CGW Gertzen ◽  
D Häussinger ◽  
H Gohlke ◽  
V Keitel
Keyword(s):  
Experimental Validation ◽  
Binding Mode

Fast and Reproducible Vascular Neointima Formation in the Hamster Carotid Artery: Effects of Trapidil and Captopril

1995 ◽  
Vol 74 (06) ◽  
pp. 1591-1596 ◽  
Author(s):  
H Matsuno ◽  
J M Stassen ◽  
M F Hoylaerts ◽  
J Vermylen ◽  
H Deckmyn
Keyword(s):  
Carotid Artery ◽  
Enzyme Inhibitor ◽  
Neointima Formation ◽  
Proliferating Cells ◽  
Dental Cement ◽  
Proliferation Indices ◽  
Experimental Drugs ◽  
The Media ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryNeointima formation was induced in the hamster carotid artery by mechanical intraluminal injury with a catheter covered with roughened dental cement. Neointimal thickening occurred as early as 7 days after denudation and further increased during the next 1 to 2 weeks. Proliferation indices of smooth muscle cells (SMCs) showed the highest proportion of proliferating cells in the media and neointima respectively 1 and 5 days after the vascular injury. Transmission and scanning electron microscopy of damaged carotid artery sections as well as immuno-histochemical stainings of von Willebrand factor (vWF) confirmed that reendothelialization was progressive and already complete on day 14, at which time the neointima formation was almost complete.In order to pharmacologically characterize this model further, the effects on neointima formation of trapidil (triazolopyrimidine), a platelet-derived growth factor (PDGF) antagonist, and captopril, an angiotensin converting enzyme inhibitor, were investigated. Trapidil administered orally twice daily at total doses of 25, 50 and 100 mg/kg/day, started 3 days prior to infliction of injury and up to 7 or 14 days after the catheterization, significantly reduced neointima formation. Captopril administered orally three times daily at a total dose of 100 mg/kg/day, equally reduced neointima formation, with 100 mg/kg/day trapidil being more effective than 100 mg/kg/day captopril 7 days after injury. When the treatment by either one of these drugs was arrested on day 7, neointima formation resumed quickly.The hamster appears to be a small, reproducible and fast model for the study of SMC proliferation, requiring only relatively small amounts of experimental drugs. The model furthermore is sensitive to substances known to reduce neointima formation in other animal models.

Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

2015 ◽  
Vol 24 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Federica Furfaro ◽  
Cristina Bezzio ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Roberto De Franchis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immunosuppressive Agents ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Proinflammatory Mediators ◽  
Experimental Drugs ◽  
New Treatments ◽  
Aggressive Clinical Course ◽  
Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

Experimental Validation of Factors Causing Flicker from Frequency Feedback Method with Step Injection of Reactive Power

2018 ◽  
Vol 138 (8) ◽  
pp. 651-658 ◽  
Author(s):  
Keisuke Shirasaki ◽  
Naotaka Okada ◽  
Kenichiro Sano ◽  
Hideki Iwatsuki
Keyword(s):  
Experimental Validation ◽  
Reactive Power ◽  
Feedback Method

Discrete Modeling and Experimental Validation of the Model of a Cantilever Flexible Beam

2015 ◽  
Vol 8 (2) ◽  
pp. 205
Author(s):  
Antonio Carlos de Assis Silva ◽  
João Bosco Gonçalves ◽  
Alvaro Manoel de Souza Soares
Keyword(s):  
Experimental Validation ◽  
Flexible Beam ◽  
Discrete Modeling
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