243 research outputs found
Potential roles of protease inhibitors in anticancer therapy
No full textIn physiological conditions, proteases are essential in carrying out biological processes such as gene expression, differentiation, and cell death. However, for their ability to degrade extracellular matrix and proteins, they are strongly associated with cancer progression. A lot of proteases have been linked with increasing tumor metastasis in different human cancers, suggesting their central functions in the metastatic process. The understanding of the proteolytic network in the tumor microenvironment is rapidly increasing because of a raised interest both in protease and in new techniques that allow for comprehensive analysis of protease activity in physiologically relevant conditions. Generally, well-established proteolytic networks consist of multiple steps of activation, several key nodes through which most signals pass, and inhibitors that can regulate activity of different points in such networks. Having a central role in several signaling pathways, proteases represent potential drug targets for a large set of diseases, especially for cancer. Protease inhibitors are compounds able to block proteases function playing a key role in cancer therapies. However, their design is a complex issue since different types of cancers use different proteases at the fluctuating stages of cancer development and no single inhibitor can be used on all classes of proteases. In this chapter, we focused our attention on protease inhibitors, describing their structure and their mechanism of action. There are several pharmaceutical strategies aimed to interfere with the proteases using different inhibitors; they may be split on basis of their mechanism of action and molecular class. In fact, protease inhibitors may be proteins, peptides, or small molecules; they are synthetic peptide-like or small molecules and, based on their inhibition process, may be divided into three main classes: reversible inhibitors, irreversible inhibitors, and engineering inhibitors
Alphavirus Nonstructural Proteases and Their Inhibitors
No full textAlphaviruses, such as Chikungunya virus, O’Nyong–Nyong virus, Ross River virus, have been widely known to cause fever, rash, and rheumatic diseases. In addition, several other alphaviruses, for instance Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, and Western equine encephalitis virus, potentially cause fatal encephalitis in humans. These diseases are considered as neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The replication process in alphaviruses depends on four nonstructural proteins, NSP1–NSP4, which are produced as a single polyprotein. Therefore, the Alphavirus-mediated diseases in humans remain challenging among the virologists worldwide. Thus researchers are trying to find out proficient approaches, including the discovery of novel chemotherapeutic agents for the possible management and treatment of infected patients. Attempts were also made to identify an active compound against alphaviruses from natural sources. The genomes of various alphaviruses have already been revealed, and the function of proteins may be predicted by homology modeling, with the known proteins of closely related viruses. With the help of this information of protein modeling and subsequent virtual screening approach, the research teams will be able to identify few potential leads. The drug discovery against various alphaviruses is still in its early stages. Moreover, consolidating the available information and making it available for the scientific community are urgent requirements to expedite the research of potential drug discovery. The current chapter describes the techniques available to prevent Alphavirus infection and to treat Alphavirus-associated malignancies. In addition, we also discuss the recent outcomes in the fields of synthetic and natural medicinal chemistry research that were solely aimed to fight against Alphavirus infection. Thus the present chapter may also help and expedite the drug discovery and development of inhibitors against nonstructural proteins of various alphaviruses
Distribution of IAT Level by Treatment status.
No full text<p>Treatment 0 refers to the control group i.e. the group which watched Tom and Jerry. Treatment 1 refers to the treatment group i.e. the group which watched the Dignity for All episode of Satya Meva Jayate.</p
Quantitative Structure—Activity Relationship Studies on Zinc‐Containing Metalloproteinase Inhibitors
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