Drug Target Insights最新文献

{"title":"Targeting <i>Streptococcus pneumoniae</i> UDP-glucose pyrophosphorylase (UGPase): in vitro validation of a putative inhibitor.","authors":"Monica Sharma,&nbsp;Swati Sharma,&nbsp;Pallab Ray,&nbsp;Anuradha Chakraborti","doi":"10.33393/dti.2020.2103","DOIUrl":"https://doi.org/10.33393/dti.2020.2103","url":null,"abstract":"<p><strong>Background: </strong>Genome plasticity of <i>Streptococcus pneumoniae</i> is responsible for the reduced efficacy of various antibiotics and capsular polysaccharide-based vaccines. Therefore, targets independent of capsular types are sought to control the pneumococcal pathogenicity. UDP-glucose pyrophosphorylase (UGPase) is one such desired candidate being responsible for the synthesis of UDP-glucose, a sugar precursor in capsular biosynthesis and metabolic Leloir pathway. Being crucial to pneumococcal pathobiology, the effect of UGPase inhibition on virulence was evaluated in vitro.</p><p><strong>Methods: </strong>A putative inhibitor, uridine diphosphate (UDP), was evaluated for effective inhibitory concentration in <i>S. pneumoniae</i> and A549 cells, its efficacy and toxicity. The effect of UDP on adherence and phagocytosis was measured in human respiratory epithelial (A549 and HEp-2) and macrophage (THP1 and J774.A.1) cell lines respectively.</p><p><strong>Results: </strong>A differential effective inhibitory concentration of UDP for UGPase inhibition was observed in <i>S. pneumoniae</i> and A549 cells, that is, 5 and 100 µM respectively. UDP treatments lowered percent cytotoxicity in pneumococcal-infected monolayers and didn't exert adverse effects on viabilities. <i>S. pneumoniae</i> adherence to host cells decreased significantly with UDP treatments. UDP induced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-8 and increased pneumococcal phagocytosis.</p><p><strong>Conclusion: </strong>Our study shows UDP-mediated decrease in the virulence of <i>S. pneumoniae</i> and demonstrates UDP as an effective inhibitor of pneumococcal UGPase.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"14 ","pages":"26-33"},"PeriodicalIF":2.7,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/4b/DTI-14-26.PMC7597228.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38553328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paradoxical bronchoconstriction caused by β₂-adrenoceptor agonists.","authors":"Khadija Ayed,&nbsp;Islam Latifa Hadj Khalifa,&nbsp;Salma Mokaddem,&nbsp;Saloua Ben Khamsa Jameleddine","doi":"10.33393/dti.2020.2188","DOIUrl":"https://doi.org/10.33393/dti.2020.2188","url":null,"abstract":"<p><strong>Introduction: </strong>Salbutamol and terbutaline are short-acting β₂ adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β₂ adrenergic agonists.</p><p><strong>Methods: </strong>This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured.</p><p><strong>Results: </strong>On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV₁ at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use.</p><p><strong>Conclusion: </strong>Salbutamol and terbutaline are generally well-tolerated β₂ adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"14 ","pages":"12-15"},"PeriodicalIF":2.7,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/4d/DTI-14-12.PMC7597223.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38553326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli: A meta-analysis report in Ethiopia.","authors":"Mengistu Abayneh, Teshale Worku","doi":"10.33393/dti.2020.2170","DOIUrl":"10.33393/dti.2020.2170","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) extended-spectrum beta-lactamase (ESBL)-producing bacterial isolates have emerged as a global threat to human health. Little is known about the overall prevalence of multidrug resistance profile and ESBL-producing gram-negative bacilli (GNB) in Ethiopia. Therefore, this meta-analysis was performed to produce proportional estimates of multidrug resistance and ESBL-producing GNB in Ethiopia. A web-based search was conducted in PubMed, Google Scholar, Research Gate, Scopus and other databases. Articles published till 2019 on the prevalence and antimicrobial resistance profiles of ESBL-producing GNB in Ethiopia were included in the study. Relevant data were extracted and statistical analysis was performed using comprehensive meta-analysis version 3.3.0 software. Publication bias was analyzed and presented with funnel plots. In this meta-analysis, the overall proportional estimate of ESBL-producing GNB was 48.9% (95% confidence interval [CI]: 0.402, 0.577). The pooled proportional estimates of ESBL-producing <i>Klebsiella pneumoniae, Escherichia coli</i> and other GNB were 61.8%, 41.2% and 42.9%, respectively. Regarding antimicrobial resistance profiles against selected drugs, the pooled proportional estimates of resistance against amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, cefotaxime, ceftazidime, tetracycline, gentamicin and ciprofloxacin was 79.0%, 78.4%, 78.0%, 72.4%, 72.7%, 58.9% and 43.8%, respectively. The pooled proportional estimates of MDR isolates were found to be 82.7% (95% CI: 0.726, 0.896), which are relatively high as compared to other countries. This highlights a need for active surveillance systems which can help understand the actual epidemiology of ESBL, aid in formulating national guidelines for proper screening of ESBL and support developing standardized approaches for managing patients colonized with ESBL.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"14 ","pages":"16-25"},"PeriodicalIF":2.7,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/f4/DTI-14-16.PMC7597226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38553327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4.","authors":"Nada M K Mabrouk,&nbsp;Dalal M Elkaffash,&nbsp;Mona Abdel-Hadi,&nbsp;Salah-ElDin Abdelmoneim,&nbsp;Sameh Saad ElDeen,&nbsp;Gihan Gewaifel,&nbsp;Khaled A Elella,&nbsp;Maher Osman,&nbsp;Nahed Baddour","doi":"10.33393/dti.2020.1548","DOIUrl":"https://doi.org/10.33393/dti.2020.1548","url":null,"abstract":"<p><strong>Background: </strong>Molecular targeted drugs are the first line of treatment of advanced hepatocellular carcinoma (HCC) due to its chemo- and radioresistant nature. HCC has several well-documented etiologic factors that drive hepatocarcinogenesis through different molecular pathways. Currently, hepatitis C virus (HCV) is a leading cause of HCC. Therefore, we included a unified cohort of HCV genotype 4-related HCCs to study the expression levels of genes involved in the insulin-like growth factor 1 receptor (IGF1R) pathway, which is known to be involved in all aspects of cancer growth and progression.</p><p><strong>Aim: </strong>Determine the gene expression patterns of IGF1R pathway genes in a cohort of Egyptian HCV-related HCCs. Correlate them with different patient/tumor characteristics. Determine the activity status of involved pathways.</p><p><strong>Methods: </strong>Total ribonucleic acid (RNA) was extracted from 32 formalin-fixed paraffin-embedded tissues of human HCV-related HCCs and 6 healthy liver donors as controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT² Profiler PCR Array for Human Insulin Signaling Pathway was done to determine significantly up- and downregulated genes with identification of most frequently coregulated genes, followed by correlation of gene expression with different patient/tumor characteristics. Finally, canonical pathway analysis was performed using the Ingenuity Pathway Analysis software.</p><p><strong>Results: </strong>Six genes - AEBP1, AKT2, C-FOS, PIK3R1, PRKCI, SHC1 - were significantly overexpressed. Thirteen genes - ADRB3, CEBPA, DUSP14, ERCC1, FRS3, IGF2, INS, IRS1, JUN, MTOR, PIK3R2, PPP1CA, RPS6KA1 - were significantly underexpressed. Several differentially expressed genes were related to different tumor/patient characteristics. Nitric oxide and reactive oxygen species production pathway was significantly activated in the present cohort, while the growth hormone signaling pathway was inactive.</p><p><strong>Conclusions: </strong>The gene expression patterns identified in this study may serve as possible therapeutic targets in HCV-related HCCs. The most frequently coregulated genes may serve to guide combined molecular targeted therapies. The IGF1R pathway showed evidence of inactivity in the present cohort of HCV-related HCCs, so targeting this pathway in therapy may not be effective.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"14 ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2020-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/f9/DTI-14-1.PMC7597224.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38556432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic Concepts in Genetics and Pharmacogenomics for Pharmacists.","authors":"Kathleen B Orrico","doi":"10.1177/1177392819886875","DOIUrl":"https://doi.org/10.1177/1177392819886875","url":null,"abstract":"<p><p>This basic review of genetic principles will aid pharmacists in preparing for their eventual role of translating gene-drug associations into clinical practice. Genes, which are stretches of deoxyribonucleic acid (DNA) contained on the 23 pairs of human chromosomes, determine the size and shape of every protein a living organism builds. Variation in pharmacogenes which encode for proteins central to drug action and toxicity serves as the basis of pharmacogenomics (PGx). Important online resources such as PharmGKB.org, cpicpgx.org, and PharmVar.org provide the clinician with curated and summarized PGx associations and clinical guidelines. As genetic testing becomes increasingly affordable and accessible, the time is now for pharmacists to embrace PGx-guided medication selection and dosing to personalize and improve the safety and efficacy of drug therapy.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"13 ","pages":"1177392819886875"},"PeriodicalIF":2.7,"publicationDate":"2019-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819886875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37453156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria.","authors":"Tasmina Hydery,&nbsp;Valerie Azzopardi Coppenrath","doi":"10.1177/1177392819857089","DOIUrl":"https://doi.org/10.1177/1177392819857089","url":null,"abstract":"<p><strong>Objective: </strong>To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations, pegvaliase injection.</p><p><strong>Data sources: </strong>Searches of MEDLINE (1946-September 1, 2018) were conducted using the terms pegvaliase and phenylalanine ammonia lyase (PAL). Additional data were obtained from the prescribing information, the product dossier obtained from the manufacturer, and Clinicaltrials.gov.</p><p><strong>Study selection and data extraction: </strong>All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed.</p><p><strong>Data synthesis: </strong>Pegvaliase is a pegylated PAL enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Blood phenylalanine levels were reduced by approximately 50% to 70% in patients receiving therapeutic doses of pegvaliase. However, most patients experienced adverse events.</p><p><strong>Conclusions and relevance: </strong>The mainstay of therapy in phenylketonuria (PKU) has historically consisted of dietary restriction of phenylalanine. Pegvaliase injection is the first Food and Drug Administration (FDA)-approved enzyme substitution therapy for patients with PKU. The therapy may be a viable option for patients with documented blood phenylalanine >600 µmol/L who have failed existing management strategies.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"13 ","pages":"1177392819857089"},"PeriodicalIF":2.7,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819857089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37377373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omalizumab as a Provoking Factor for Venous Thromboembolism","authors":"C. Oblitas, F. Galeano-Valle, Laura Vela-De La Cruz, J. del Toro-Cervera, P. Demelo-Rodríguez","doi":"10.1177/1177392819861987","DOIUrl":"https://doi.org/10.1177/1177392819861987","url":null,"abstract":"A 43-year-old man with a history of severe extrinsic allergic asthma treated with once-monthly omalizumab (600 mg) for the last 15 months. He presented to the emergency room with a 2-week history of right lower limb pain and chest pleuritic pain. Computed tomography pulmonary angiography showed bilateral pulmonary embolism with right-sided pulmonary infarction and ultrasound of right lower limb confirmed distal deep vein thrombosis. No other known risk factors were identified. Treatment with omalizumab was stopped during hospitalization. The Naranjo Adverse Drug Reaction (ADR) Probability Scale classifies this as a probable ADR (score of 6). Omalizumab is a humanized monoclonal anti-IgE antibody indicated for the treatment of persistent moderate-to-severe asthma and certain chronic refractory urticaria. The EXCELS study (The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma), a postmarketing observational cohort study to assess clinical safety profile of omalizumab, showed a significant increase in venous thromboembolism. In conclusion, omalizumab has been associated with arterial and venous thromboembolic events, although the evidence is not definitive.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819861987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47878471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vernakalant in Atrial Fibrillation: A Relatively New Weapon in the Armamentarium Against an Old Enemy","authors":"A. Kossaify","doi":"10.1177/1177392819861114","DOIUrl":"https://doi.org/10.1177/1177392819861114","url":null,"abstract":"Atrial fibrillation is the most common sustained cardiac arrhythmia, and its prevalence is increasing with age; also it is associated with significant morbidity and mortality. Rhythm control is advised in recent-onset atrial fibrillation, and in highly symptomatic patients, also in young and active individuals. Moreover, rhythm control is associated with lower incidence of progression to permanent atrial fibrillation. Vernakalant is a relatively new anti-arrhythmic drug that showed efficacy and safety in recent-onset atrial fibrillation. Vernakalant is indicated in atrial fibrillation (⩽7 days) in patients with no heart disease (class I, level A) or in patients with mild or moderate structural heart disease (class IIb, level B). Moreover, Vernakalant may be considered for recent-onset atrial fibrillation (⩽3 days) post cardiac surgery (class IIb, level B). Although it is mainly indicated in patients with recent-onset atrial fibrillation and with no structural heart disease, it can be given in moderate stable cardiac disease as alternative to Amiodarone. Similarly to electrical cardioversion, pharmacological cardioversion requires a minimal evaluation and cardioversion should be included in a comprehensive management strategy for better outcome.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"13 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819861114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42796524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies","authors":"Aimi Syamima Abdul Manap, S. Vijayabalan, P. Madhavan, Y. Y. Chia, A. Arya, E. H. Wong, Farzana Rizwan, U. Bindal, Shajan Koshy","doi":"10.1177/1177392819866412","DOIUrl":"https://doi.org/10.1177/1177392819866412","url":null,"abstract":"Alzheimer disease is a neurodegenerative disease that is signified by cognitive decline, memory loss, and erratic behavior. Till date, no cure for Alzheimer exists and the current Alzheimer medications have limited effectiveness. However, herbal medicines may slow down the disease’s progression, which may hopefully reduce the number of cases in the years to come. Numerous studies have been done on characterizing the neuroprotective properties from plants belonging to Scrophulariaceae family, particularly Bacopa monnieri and its polyphenolic compounds known as bacosides. This review presents the findings on bacosides in therapeutic plants and their impact on Alzheimer disease pathology. These reports present data on the clinical, cellular activities, phytochemistry, and biological applications that may be used in new drug treatment for Alzheimer disease.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819866412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47389478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DRESS Syndrome and Daclizumab Failure-Were Potentially Dangerous Signs Missed in Clinical Trials?","authors":"Jagannadha Avasarala","doi":"10.1177/1177392818785136","DOIUrl":"10.1177/1177392818785136","url":null,"abstract":"<p><p>The US Food and Drug Administration (FDA) approved Zinbryta, an interleukin-2 receptor blocking antibody (daclizumab; Biogen and AbbVie) for the treatment of adults with relapsing forms of multiple sclerosis (MS) in May, 2016. It was also approved by the European Union in July, 2016. Zinbryta is a long-acting, self-administered monthly injection that was branded as a new MS drug for patients who needed a \"new option for treatment.\" It blocks interleukin-2 receptor alpha (CD25) and modulates T-cell expansion. The drug was withdrawn from the market in March, 2018 following 12 reports from Germany (9), United States (2), and Spain (1) following the development of \"inflammatory encephalitis and meningoencephalitis\" in patients on Zinbryta. Although cases of hepatotoxicity made news with Zinbryta earlier along this drug's postmarketing journey in the treatment of patients with MS, the European Medicines Agency (EMA) ordered a review of the risks of hepatotoxicity with Zinbryta use June, 2017; this analysis will focus on the pharmacovigilance data concerning the central nervous system (CNS) complications. The details of the CNS complications have been elucidated by EMA. Every drug failure provides an opportunity for learning, but it is also noteworthy that no FDA-approved MS drug in modern times has met with such an untimely, sudden, and inglorious exit. This should serve as a cautionary tale for all clinicians who use \"newer MS drugs\" that have mushroomed in recent memory following a flurry of recent FDA approvals.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"12 ","pages":"1177392818785136"},"PeriodicalIF":2.7,"publicationDate":"2018-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392818785136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36318019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}