Epidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein that constitutes one of the four members of ErbB family of tyrosine kinase receptors. Activation of EGFR leads to autophosphorylation of receptor tyrosine kinase that initiates a cascade of downstream signaling pathways involved in regulating cellular proliferation, differentiation, and survival. EGFR is abnormally activated by various mechanisms like receptor overexpression, mutation, ligand-dependent receptor dimerization, ligand-independent activation and is associated with the development of variety of human cancers. EGFR inhibition is one of the key targets for cancer chemotherapy. Approval of tyrosine kinase inhibitors such as erlotinib, gefitinib, and lapatinib for the treatment of non-small cell lung cancer led to tremendous development of novel EGFR inhibitors in the last decade. Diverse class of chemical compounds from the synthetic origin has been extensively studied. This review highlights the various classes of synthetically derived molecules which have been reported in the last few years as potential EGFR and EGFR/ErbB-2 dual inhibitors. A brief synthetic methodology to access these compounds has been highlighted along with the SAR. We strongly believe that this review will provide a platform to the synthetic chemists and biologists to design and synthesize new and potent compounds that inhibit EGFR and ErbB-2.
Benzothiazole is a privileged heterocyclic scaffold having a benzene ring fused with a five-membered thiazole ring. This moiety has attracted considerable attention because of its wide range of pharmacological activities such as antitubercular, antimicrobial, antimalarial, anticonvulsant, anthelmintic, analgesic, anti-inflammatory, antidiabetic, antitumor activity, etc. In the last few years, some novel benzothiazoles have been developed with varied biological activities. To access this scaffold in high yield and to introduce diversity, a variety of new synthetic methods have been invented. In this review, we highlight the development of novel benzothiazoles for various biological activities along with the best synthetic protocols for their synthesis.
Our findings in a North American cohort are in agreement with studies from Asia and Europe suggesting that H. pylori infection decreases the prevalence of obesity in children. Further work to characterize the extent and nature of this relationship is warranted.
The increasing prevalence of worldwide obesity has emerged as a major risk factor for type 2 diabetes (T2D), hepatosteatosis, and cardiovascular disease. Accumulating evidence indicates that obesity has strong inflammatory underpinnings tightly linked to the development of metabolic diseases. However, the molecular mechanisms by which obesity induces aberrant inflammation associated with metabolic diseases are not yet clearly defined. Recently, RNAs have emerged as important regulators of stress responses and metabolism. RNAs are subject to changes in modification status, higher-order structure, and cellular localization; all of which could affect the affinity for RNA-binding proteins (RBPs) and thereby modify the RNA-RBP networks. Proper regulation and management of RNA characteristics are fundamental to cellular and organismal homeostasis, as well as paramount to health. Identification of multiple single nucleotide polymorphisms (SNPs) within loci of fat mass- and obesity-associated protein (FTO) gene, an RNA demethylase, through genome-wide association studies (GWAS) of T2D, and functional assessments of FTO in mice, support the concept that disruption in RNA modifications leads to the development of human diseases including obesity and metabolic disorder. In obesity, dynamic alterations in modification and localization of RNAs appear to modulate the RNA-RBP networks and activate proinflammatory RBPs, such as double-stranded RNA (dsRNA)-dependent protein kinase (PKR), Toll-like receptor (TLR) 3 and TLR7, and RNA silencing machinery. These changes induce aberrant inflammation and the development of metabolic diseases. This review will describe the current understanding of the underlying causes of these common and altered characteristics of RNA-RBP networks which will pave the way for developing novel approaches to tackle the pandemic issue of obesity.
A thermostable glucoamylase (GA) showed optimum activity at 70 degrees C and pH 5.0. It was highly stable at pH 7.0. The half-life of the enzyme at pH 7.0 was 13, 8, and 3 h 40 min at 60, 65, and 70 degrees C respectively. The residual activity of the enzyme sample incubated at 5 psi (110 degrees C) for 30 min was about 32% of the control set (incubated at 4 degrees C), while no activity was observed at 10 and 15 psi. The thermostability of the enzyme was enhanced twofold in the presence of 0.5% (w/v) starch at 5 psi. Thin-layer chromatography indicated that this enzyme is a GA.
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