12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Current Status of COVID-19 Therapies and Drug Repositioning Applications.

iScience. 2020 Jun 20;23(7):101303

Authors: Altay O, Mohammadi E, Lam S, Turkez H, Boren J, Nielsen J, Uhlen M, Mardinoglu A

Abstract
The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.

PMID: 32622261 [PubMed - as supplied by publisher]

High-throughput Algorithm for Discovering New Drug Indications by Utilizing Large-Scale Electronic Medical Record data.

Clin Pharmacol Ther. 2020 Jul 04;:

Authors: Kim DH, Lee J, Kim YG, Lee Y, Seo DW, Hwa Lee K, Lee JH, Kim WS, Kim YH, Oh JS

Abstract
Drug repositioning is an effective way to mitigate the production problem in the pharmaceutical industry. Electronic medical record (EMR) databases harbor a large amount of data on drug prescriptions and laboratory test results and may thus be useful for finding new indications for existing drugs. Here, we present a novel high-throughput data-driven algorithm that identifies and prioritizes drug candidates that show significant effects on specific clinical indicators by utilizing large-scale EMR data. We chose four laboratory tests as clinical indicators: hemoglobin A1c (HbA1c), low-density lipoprotein (LDL) cholesterol, triglycerides (TG), and high-density lipoprotein (HDL) cholesterol. From a 5-year EMR database, we generated datasets consisting of paired data with averaged measurement values during on and off each drug in each patient, adjusted for co-administered drug effects at each timepoint, and applied one sample T-test with the Bonferroni correction for statistical analysis. Among 1774 drugs, 45 were associated with increases in HDL cholesterol, and 41, 146, and 65 were associated with reductions in HbA1c, LDL cholesterol, and TG, respectively. We compared the list of candidate drugs with that of drugs indicated for relevant clinical conditions and found that the algorithm had high values for both sensitivity (range, 0.95-1.00) and negative predictive value (range, 0.95-1.00). Our algorithm was able to rediscover well-known drugs that are used for diabetes and dyslipidemia while revealing potential candidates without current indications but have shown promising results in the literature. Our algorithm may facilitate the repositioning of drugs with proven safety profiles.

PMID: 32621536 [PubMed - as supplied by publisher]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/03

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Lessons from SARS-CoV-2 Pandemic: Evolution, Disease Dynamics and Future.

Biology (Basel). 2020 Jun 26;9(6):

Authors: Pandey S, Yadav B, Pandey A, Tripathi T, Khawary M, Kant S, Tripathi D

Abstract
The COVID-19 pandemic is rising at an unprecedented rate. The surging number of deaths every day, global lockdown and travel restrictions have resulted in huge losses to society. The impact is massive and will leave a historical footprint. The Spanish Flu of 1918, which was the last pandemic that had a similar impact, was shadowed under the consequences of World War I. All the brilliance, strength and economies of countries worldwide are aimed at fighting the COVID-19 pandemic. The knowledge about coronavirus dynamics, its nature and epidemiology are expanding every day. The present review aims to summarize the structure, epidemiology, symptoms, statistical status of the disease status, intervention strategies and deliberates the lessons learnt during the pandemic. The intervention approaches, antiviral drug repurposing and vaccine trials are intensified now. Statistical interpretations of disease dynamics and their projections may help the decision-makers.

PMID: 32604825 [PubMed]

Inhibition of Bruton's tyrosine kinase regulates macrophage NF-κB and NLRP3 inflammasome activation in metabolic inflammation.

Br J Pharmacol. 2020 Jul 01;:

Authors: Purvis GSD, Collino M, Aranda-Tavio H, Chiazza F, O'Riordan CE, Zeboudj L, Mohammad S, Collotta D, Verta R, Guisot NES, Bunyard P, Yaqoob MM, Greaves DR, Thiemermann C

Abstract
BACKGROUND AND PURPOSE: Currently there are limited medicines available for the treatment of metabolic inflammation in diseases such as obesity and type 2 diabetes (T2D). Although initially associated with B-ells, Bruton's tyrosine kinase (BTK) is present in a wide variety of cells including monocytes and macrophages, and has been implicated in the regulation of the NF-κB and NLRP3 inflammasome activity.
EXPERIMENTAL APPROACH: Using in vivo models of chronic inflammation [high-fat-diet (HFD) feeding] and in vitro assays in primary murine and human macrophages we investigated if ibrutinib, an FDA approved medicine that targets BTK, may represent a novel anti-inflammatory drug for the use in treating metabolic inflammation.
KEY RESULTS: HFD feeding was associated with increased BTK expression and activation, which was significantly correlated with monocyte/macrophage accumulation in the liver, adipose tissue and kidney. Treatment of mice fed HFD with ibrutinib inhibited the activation of BTK and reduced monocyte/macrophage recruitment to the liver, adipose tissue and kidney. Reduced inflammatory gene expression associated with decreased activation of NF-κB and the NLRP3 inflammasome in vivo. As a result, ibrutinib treated mice fed HFD had improved glycaemic control through restored signalling by the IRS-1/Akt/GSK-3β pathway; protecting mice against the development of hepatosteatosis and proteinuria. We show that inhibition of BTK reduces activation of NF-κB and the NLRP3 inflammasome specifically in primary murine and human macrophages; which are the primary target of ibrutinib in vivo in the setting of metabolic inflammation.
CONCLUSIONS AND IMPLICATIONS: In the present study we provide 'proof of concept' evidence that BTK is a novel therapeutic target for the treatment of diet -metabolic inflammation. Ibrutinib may be a candidate for drug repurposing as an anti-inflammatory for the treatment of metabolic inflammation in T2D and microvascular disease.

PMID: 32608058 [PubMed - as supplied by publisher]

COVID-19 treatment: Combining anti-inflammatory and antiviral therapeutics using a network-based approach.

Cleve Clin J Med. 2020 Jun 30;:

Authors: Cheng F, Rao S, Mehra R

Abstract
To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options for COVID-19. We discuss one treatment strategy that combines anti-inflammatory (melatonin) and antiviral (toremifene) agents for patients infected with SARS-CoV-2 from network medicine-based findings. We also describe the pathobiology and immunologic characteristics of COVID-19 and highlight the rationale of combination drug treatment to rescue the pulmonary and cardiovascular conditions resulting from COVID-19. A preliminary analysis reveals a high potential for the synergistic effects of melatonin and toremifene to reduce viral infection and replication, and the aberrant host inflammatory responses, offering strong biologic plausibility as an effective therapy for COVID-19.

PMID: 32606050 [PubMed - as supplied by publisher]

High content drug screening for Fanconi anemia therapeutics.

Orphanet J Rare Dis. 2020 Jun 30;15(1):170

Authors: Montanuy H, Camps-Fajol C, Carreras-Puigvert J, Häggblad M, Lundgren B, Aza-Carmona M, Helleday T, Minguillón J, Surrallés J

Abstract
BACKGROUND: Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection for solid tumors. Therefore, there is still an urgent need for new therapeutic options. With this aim, we developed a novel high-content cell-based screening assay to identify drugs with therapeutic potential in FA.
RESULTS: A TALEN-mediated FANCA-deficient U2OS cell line was stably transfected with YFP-FANCD2 fusion protein. These cells were unable to form fluorescent foci or to monoubiquitinate endogenous or exogenous FANCD2 upon DNA damage and were more sensitive to mitomycin C when compared to the parental wild type counterpart. FANCA correction by retroviral infection restored the cell line's ability to form FANCD2 foci and ubiquitinate FANCD2. The feasibility of this cell-based system was interrogated in a high content screening of 3802 compounds, including a Prestwick library of 1200 FDA-approved drugs. The potential hits identified were then individually tested for their ability to rescue FANCD2 foci and monoubiquitination, and chromosomal stability in the absence of FANCA.
CONCLUSIONS: While, unfortunately, none of the compounds tested were able to restore cellular FANCA-deficiency, our study shows the potential capacity to screen large compound libraries in the context of Fanconi anemia therapeutics in an optimized and cost-effective platform.

PMID: 32605631 [PubMed - in process]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/07/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Evaluation of gene-drug common module identification methods using pharmacogenomics data.

Brief Bioinform. 2020 Jun 26;:

Authors: Huang J, Chen J, Zhang B, Zhu L, Cai H

Abstract
Accurately identifying the interactions between genomic factors and the response of cancer drugs plays important roles in drug discovery, drug repositioning and cancer treatment. A number of studies revealed that interactions between genes and drugs were 'many-genes-to-many drugs' interactions, i.e. common modules, opposed to 'one-gene-to-one-drug' interactions. Such modules fully explain the interactions between complex biological regulatory mechanisms and cancer drugs. However, strategies for effectively and robustly identifying the underlying common modules among pharmacogenomics data remain to be improved. In this paper, we aim to provide a detailed evaluation of three categories of state-of-the-art common module identification techniques from a machine learning perspective, including non-negative matrix factorization (NMF), partial least squares (PLS) and network analyses. We first evaluate the performance of six methods, namely SNMNMF, NetNMF, SNPLS, O2PLS, NSBM and HOGMMNC, using two series of simulated data sets with different noise levels and outlier ratios. Then, we conduct experiments using a real world data set of 2091 genes and 101 drugs in 392 cancer cell lines and compare the real experimental results from the aspect of biological process term enrichment, gene-drug and drug-drug interactions. Finally, we present interesting findings from our evaluation study and discuss the advantages and drawbacks of each method. Supplementary information: Supplementary file is available at Briefings in Bioinformatics online.

PMID: 32591780 [PubMed - as supplied by publisher]

Repurposing anthelmintic agents to eradicate resistant leukemia.

Blood Cancer J. 2020 Jun 26;10(6):72

Authors: Mezzatesta C, Abduli L, Guinot A, Eckert C, Schewe D, Zaliova M, Vinti L, Marovca B, Tsai YC, Jenni S, Aguade-Gorgorio J, von Stackelberg A, Schrappe M, Locatelli F, Stanulla M, Cario G, Bourquin JP, Bornhauser BC

Abstract
Despite rapid progress in genomic profiling in acute lymphoblastic leukemia (ALL), identification of actionable targets and prediction of response to drugs remains challenging. To identify specific vulnerabilities in ALL, we performed a drug screen using primary human ALL samples cultured in a model of the bone marrow microenvironment combined with high content image analysis. Among the 2487 FDA-approved compounds tested, anthelmintic agents of the class of macrocyclic lactones exhibited potent anti-leukemia activity, similar to the already known anti-leukemia agents currently used in induction chemotherapy. Ex vivo validation in 55 primary ALL samples of both precursor B cell and T-ALL including refractory relapse cases confirmed strong anti-leukemia activity with IC50 values in the low micromolar range. Anthelmintic agents increased intracellular chloride levels in primary leukemia cells, inducing mitochondrial outer membrane depolarization and cell death. Supporting the notion that simultaneously targeting cell death machineries at different angles may enhance the cell death response, combination of anthelmintic agents with the BCL-2 antagonist navitoclax or with the chemotherapeutic agent dexamethasone showed synergistic activity in primary ALL. These data reveal anti-leukemia activity of anthelmintic agents and support exploiting drug repurposing strategies to identify so far unrecognized anti-cancer agents with potential to eradicate even refractory leukemia.

PMID: 32591499 [PubMed - as supplied by publisher]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Drug repositioning based on the target microRNAs using bilateral-inductive matrix completion.

Mol Genet Genomics. 2020 Jun 24;:

Authors: Deepthi K, Jereesh AS

Abstract
Identifying the cause-and-effect mechanism behind the drug-disease associations is a challenging task. Recent studies indicate that microRNAs (miRNAs) play critical roles in human diseases. Targeting specific miRNAs with drugs to treat diseases provides a new aspect for drug repositioning. Drug repositioning provides a way to identify new clinical applications for approved drugs. Drug discovery is expensive and complicated. Therefore, computational methods are necessary for predicting the potential associations between drugs and diseases based on the target miRNAs. Our approach bilateral-inductive matrix completion (BIMC) performed two rounds of inductive matrix completion algorithm, one on the drug-miRNA and another on the miRNA-disease, association matrices, and integrated the results for predicting the drug-disease relationships through the target miRNAs. The fundamental idea of inductive matrix completion (IMC) is to fill the unknown entries of the association matrices by utilizing existing associations and side information. In our study, the integrated similarities of drugs, miRNAs, and diseases were utilized as side information. Our method predicts drug-miRNA and miRNA-disease associations, as intermediate results. To estimate the performance of our approach, we conducted leave-one-out cross-validation (LOOCV) experiments. The method could achieve AUC scores of 0.792, 0.759, and 0.791 in drug-disease, drug-miRNA, and miRNA-diseases association predictions. The results and case studies indicate the prediction ability of our method, and it is superior to previous models with high robustness. The proposed approach predicts new drug-disease relationships and the causal miRNAs. The top predicted relationships are the promising candidates, and they are released for further biological tests.

PMID: 32583015 [PubMed - as supplied by publisher]

Prediction of Drug-Target Interactions From Multi-Molecular Network Based on Deep Walk Embedding Model.

Front Bioeng Biotechnol. 2020;8:338

Authors: Chen ZH, You ZH, Guo ZH, Yi HC, Luo GX, Wang YB

Abstract
Predicting drug-target interactions (DTIs) is crucial in innovative drug discovery, drug repositioning and other fields. However, there are many shortcomings for predicting DTIs using traditional biological experimental methods, such as the high-cost, time-consumption, low efficiency, and so on, which make these methods difficult to widely apply. As a supplement, the in silico method can provide helpful information for predictions of DTIs in a timely manner. In this work, a deep walk embedding method is developed for predicting DTIs from a multi-molecular network. More specifically, a multi-molecular network, also called molecular associations network, is constructed by integrating the associations among drug, protein, disease, lncRNA, and miRNA. Then, each node can be represented as a behavior feature vector by using a deep walk embedding method. Finally, we compared behavior features with traditional attribute features on an integrated dataset by using various classifiers. The experimental results revealed that the behavior feature could be performed better on different classifiers, especially on the random forest classifier. It is also demonstrated that the use of behavior information is very helpful for addressing the problem of sequences containing both self-interacting and non-interacting pairs of proteins. This work is not only extremely suitable for predicting DTIs, but also provides a new perspective for the prediction of other biomolecules' associations.

PMID: 32582646 [PubMed]

Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties.

Clin Pharmacokinet. 2020 06;59(6):659-669

Authors: Smit C, Peeters MYM, van den Anker JN, Knibbe CAJ

Abstract
Since in vitro studies and a preliminary clinical report suggested the efficacy of chloroquine for COVID-19-associated pneumonia, there is increasing interest in this old antimalarial drug. In this article, we discuss the pharmacokinetics and safety of chloroquine that should be considered in light of use in SARS-CoV-2 infections. Chloroquine is well absorbed and distributes extensively resulting in a large volume of distribution with an apparent and terminal half-life of 1.6 days and 2 weeks, respectively. Chloroquine is metabolized by cytochrome P450 and renal clearance is responsible for one third of total clearance. The lack of reliable information on target concentrations or doses for COVID-19 implies that for both adults and children, doses that proved effective and safe in malaria should be considered, such as 'loading doses' in adults (30 mg/kg over 48 h) and children (70 mg/kg over 5 days), which reported good tolerability. Here, plasma concentrations were < 2.5 μmol/L, which is associated with (minor) toxicity. While the influence of renal dysfunction, critical illness, or obesity seems small, in critically ill patients, reduced absorption may be anticipated. Clinical experience has shown that chloroquine has a narrow safety margin, as three times the adult therapeutic dosage for malaria can be lethal when given as a single dose. Although infrequent, poisoning in children is extremely dangerous where one to two tablets can potentially be fatal. In conclusion, the pharmacokinetic and safety properties of chloroquine suggest that chloroquine can be used safely for an acute virus infection, under corrected QT monitoring, but also that the safety margin is small, particularly in children.

PMID: 32306288 [PubMed - indexed for MEDLINE]

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.