{"title":"Osteopontin.","authors":"M. Chellaiah, K. Hruska","doi":"10.32388/7se6au","DOIUrl":"https://doi.org/10.32388/7se6au","url":null,"abstract":"Although osteopontin (OP) has been shown to play a role in bone mineralization and to mediate bone cell adhesion, its function in other tissues is not yet known. The sequences of OP from seven species have been reported; some of the sequences that are conserved in all seven species and their functions are mentioned. The biochemical structure of OP and the functional properties of its motifs make OP a strong candidate for regulating mineralization and/or mediating local cell dynamics. In addition to its role in mineralization, OP has also been shown to promote migration of smooth muscle cells and macrophages. OP expression is high in many tumors, and it correlates with the metastatic potential in some instances. Abundant OP has also been found in human tissue specimens from patients with clinical tuberculosis and in other granulomatous diseases. Experimental approaches in the authors' laboratory have focused on the role of OP as an autocrine motility factor in osteoclasts and human melanoma cell lines; their results suggest that posttranslational modification (phosphorylation) of OP is important in its biological functions.","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"98 1","pages":"350-5"},"PeriodicalIF":0.0,"publicationDate":"2020-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85764811","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":"Trends in medicinal chemistry.","authors":"K. Chou","doi":"10.3390/MOL2NET-03-04615","DOIUrl":"https://doi.org/10.3390/MOL2NET-03-04615","url":null,"abstract":"The Society for Medicines Research held a meeting on Trends in Medicinal Chemistry on November 30, 2000, in Stevenage, U.K., with the goal of alerting researchers to emerging areas of chemistry and novel classes of compounds likely to lead to new approaches to the treatment of disease. Speakers from nine pharmaceutical companies described areas of research that included phosphodiesterase inhibitors, adenosine receptor ligands, VEGF RTK inhibitors, RNA-protein interaction inhibitors, NMT inhibitors, anti-HCV agents and antidepressants.","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"1 1","pages":"628-33"},"PeriodicalIF":0.0,"publicationDate":"2017-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77271322","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":"Molecule of the Month.","authors":"R. Jacobs, J. Plattner, R. Don","doi":"10.2174/1568026611107011301","DOIUrl":"https://doi.org/10.2174/1568026611107011301","url":null,"abstract":"","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"5 1","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2011-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88827858","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":"The significance of GlgE as a new target for tuberculosis.","authors":"Rainer Kalscheuer, William R Jacobs","doi":"10.1358/dnp.2010.23.10.1534855","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1534855","url":null,"abstract":"<p><p>Largely neglected by the industrialized world for decades, tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, has made a fulminant return to the public health agenda as a major global health threat. The worsening of the TB pandemic is driven by the rapid emergence of multidrug-resistant and extensively drug-resistant M. tuberculosis strains, which are virtually untreatable with current chemotherapies. The search for new strategies to combat such resistant strains is of paramount importance for control of the TB pandemic. In searching for new vulnerable processes in M. tuberculosis to enable the rational design of more efficient anti-TB chemotherapy, a novel class of antimycobacterial drug targets has recently been discovered; it is represented by GlgE, an essential maltosyltransferase that elongates linear α-glucans as part of a synthetic lethal biosynthetic pathway. Inactivation of GlgE causes accumulation of a toxic phosphosugar intermediate, maltose 1-phosphate, which drives the bacilli into a suicidal self-poisoning cycle that elicits a complex stress profile, eventually resulting in DNA damage and death of M. tuberculosis. GlgE combines many favorable properties that make it a highly attractive novel drug target for chemotherapy of TB.</p>","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"619-24"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1358/dnp.2010.23.10.1534855","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555127","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":"Trioxaquines: hybrid molecules for the treatment of malaria.","authors":"Shikha S Chauhan, Moni Sharma, Prem M S Chauhan","doi":"10.1358/dnp.2010.23.10.1468390","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1468390","url":null,"abstract":"Artemisinin, with its 1,2,4-trioxane as active motif, is now the first-line treatment for multidrug-resistant malaria. The endoperoxide ring is essential for the antimalarial activity of artemisinin. Based on its mechanism of action, new hybrid molecules named trioxaquines with a dual mode of action have been designed. Trioxaquines are made by the covalent attachment of a trioxane, having alkylating ability, to a quinoline, known to easily penetrate within infected erythrocytes. This review discusses the importance of various hybrid molecules of artemisinin and 4-aminoquinoline in the treatment of malaria and the evolution of a trioxaquine hybrid as a promising antimalarial drug candidate.","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"632-46"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555130","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":"Are we living in the end of the blockbuster drug era?","authors":"Bikash Debnath, Laith Q Al-Mawsawi, Nouri Neamati","doi":"10.1358/dnp.2010.23.10.1506088","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1506088","url":null,"abstract":"<p><p>For the last two decades, we have seen remarkable growth in the pharmaceutical industry. This growth has mainly been due to the approximately 100 new blockbuster drugs, such as Lipitor® (atorvastatin) and Plavix® (clopidogrel). More than half of the revenue of major pharmaceutical companies and above one-third of the total pharmaceutical revenues came from the sales of these blockbuster drugs. Questions concerning the fate of these blockbuster drugs are beginning to surface as they are approaching their patent expiration dates, and as they are expected to face significant competition from generic versions. Branded drugs with more than USD 120 billion in sales (as of 2008) are expected to lose their patent protection in the next 3 to 4 years, while the less expensive generic versions are ready to enter the market. It is plausible that a major paradigm shift in our thinking is needed to stay innovative, competitive and economically feasible in this new era of drug development. A new wave of innovations is expected to boost the blockbuster regime. Herein, we discuss the different threats facing the branded monopoly, as well as some of the hopeful expectations for the blockbuster drug.</p>","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"670-84"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555134","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}
Jia Wei, Li Xie, Miquel Taron, Rafael Rosell, Baorui Liu
{"title":"Epigenetic alterations of tumor marker microRNAs: towards new cancer therapies.","authors":"Jia Wei, Li Xie, Miquel Taron, Rafael Rosell, Baorui Liu","doi":"10.1358/dnp.2010.23.10.1560143","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1560143","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are a class of short noncoding RNAs that participate in mastering the balance of gene-regulating networks. By targeting and controlling expression of messenger RNA, miRNAs can control highly complex signal transduction pathways and other biological pathways. Unique aberrant expression of miRNA at each stage of cancer development suggests that miRNA could play a novel role in cancer diagnosis and therapeutic strategies. Accumulated information on epigenetic modification of miRNA suggests a promising platform for miRNA in cancer therapy. Clinical applications exploiting the understanding of miRNA's function will be the next great challenge in cancer research.</p>","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"655-61"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555132","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":"Molecule of the Month. TAK-875.","authors":"","doi":"10.1358/dnp.2010.23.10.1560199","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1560199","url":null,"abstract":"","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"667"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555133","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}
Lars Frelin, Anette Brass, Gustaf Ahlén, Erwin Daniel Brenndörfer, Margaret Chen, Matti Sällberg
{"title":"Electroporation: a promising method for the nonviral delivery of DNA vaccines in humans?","authors":"Lars Frelin, Anette Brass, Gustaf Ahlén, Erwin Daniel Brenndörfer, Margaret Chen, Matti Sällberg","doi":"10.1358/dnp.2010.23.10.1513492","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1513492","url":null,"abstract":"<p><p>The without a doubt major obstacle for making DNA vaccines a commercial success is delivery. If delivery cannot be made simple, cheap and effective, DNA vaccines may not become a viable option for human use. Numerous clinical trials have confirmed that a standard needle and syringe simply do not do the job, i.e., delivering the DNA payload inside the cell. Having recognized this shortcoming, investigators have developed several new approaches for DNA vaccine delivery. In particular, new types of delivery devices, originally intended for in vitro use, have been applied for in vivo delivery. These include particle bombardment or biolistic delivery, and in vivo electroporation (EP). Importantly, both techniques seem to overcome the size barrier, meaning that they work in both mice and larger animals. In vivo EP has the key features of improved DNA uptake, increased antigen expression and a local inflammation. These factors are essential to make DNA vaccines effective in a larger host. Early data from clinical trials with DNA vaccines delivered by in vivo EP are cautiously promising. Thus, we may be entering a new era of DNA vaccination where we start to see clinical effects in humans; however, these may also be accompanied by side effects, as the vaccines become more effective.</p>","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"647-53"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555131","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":"Inhibition of potassium currents as a pharmacologic target for investigation in chronic lymphocytic leukemia.","authors":"Bella Biderman, Andrey Marakhonov, Mikhail Skoblov, Aybike Birerdinc, Elizabeth Nohelty, Sandra Page, Vasiliy Khomenkov, Vikas Chandhoke, Andrey Sudarikov, Eugene Nikitin, Ancha Baranova","doi":"10.1358/dnp.2010.23.10.1507740","DOIUrl":"https://doi.org/10.1358/dnp.2010.23.10.1507740","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) represents 22-30% of all leukemia cases, thus being the most commonly diagnosed form of adult leukemia in the Western world. On a cellular level, the disease progresses due to the prolonged survival of B-cell CLL cells arrested in the G₀ stage of the cell cycle. The current standard treatment for CLL is a combination regimen containing purine analogues and monoclonal antibodies. Although response rates to such regimens in previously untreated patients are high, patients with CLL invariably experience relapse and often acquire high-risk chromosomal abnormalities. Therefore, the search for novel avenues in CLL treatment is warranted. In this manuscript, we will describe theoretical premises and some preliminary data making the case for inhibitors of the potassium currents as possible proapoptotic agents that warrant investigation as a potential pharmacologic target in CLL.</p>","PeriodicalId":11325,"journal":{"name":"Drug news & perspectives","volume":"23 10","pages":"625-31"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555129","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}
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