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Sorafenib Tosylate is a multikinase inhibitor

Hepatitis C virus (HCV) was discovered in 1989 . It was found to be responsible for the vast majority of so-called chronic non-A, non-B hepatitis and cryptogenetic liver diseases . In adults, Sorafenib acute HCV infection leads to chronic infection in approximately 80% of cases. Chronic HCV infection is responsible for chronic hepatitis,which is complicated by cirrhosis in approximately 20% of cases. Patients with cirrhosis are exposed to life-threatening complications, including end-stage liver disease, esophageal varices hemorrhage and the development of hepatocellular carcinoma, which occurs at an incidence of 4%- 5% per year in these patients . Approximately 120-130 million individuals are chronically infected with HCV worldwide . Chronic HCV infection has become the leading cause of hepatocellular carcinoma (primary liver cancer) and the first indication of liver transplantation in industrialized countries . Six MDV3100 genotypes (1 to 6) and a number of subtypes have been described. Genotype 1 (subtypes 1a and 1b) is by far the most frequent genotype worldwide . Unlike other known chronic viral infections, HCV infection is curable by therapy.
Cure of infection is characterized by the sustained virological response, defined as undetectable HCV RNA in peripheral blood by means of sensitive molecular biology-based techniques. Until recently, treatment of chronic hepatitis C was based on the combination of a pegylated form of interferon (IFN)-a (pegylation improves the pharmacokinetic and pharmacodynamic properties and enhances the antiviral potency of IFN) and ribavirin [8-10]. This combination cures approximately 80% of infections in patients infected with HCV genotypes 2 or 3, but only 40%-50% Tofacitinib in patients infected with genotypes 1 or 4. This emphasizes the need for more efficient antiviral strategies. Over the past 10 years, a number of models have been developed to study the HCV lifecycle and screen for potential HCV inhibitors . These models include cellfree enzyme assays for the HCV NS3-4A protease and RNA-dependent RNA polymerase, hepatoma cell lines harboring subgenomic and genomic replicons (nucleicacids capable of autonomous replication), an infectious cell culture system (limited to genotype 2a), and humanized mouse models infectable by HCV. They led to the PI3K inhibition development of antiviral agents that specifically target a viral function, now collectively termed ??direct acting antivirals.
In addition, host-targeted agents that inhibit HCV replication are also in development. This article describes the direct acting antivirals that have recently been approved and direct acting antivirals and host-targeted agents that have been tested inHCV-infected patients and discusses their current paths of clinical development: with or without IFN-a. New HCV drugs in development In principle, every step of the gsk3 HCV lifecycle, including receptor binding, endocytosis, fusion, uncoating, translation, polyprotein processing, RNA replication, virion assembly, maturation, transport and release, can be a target for new anti-HCV drugs . Thus far, drugs targeting two major steps of the HCV lifecycle have reached clinical development. They include inhibitors of the HCV NS3-4A protease that block polyprotein processing and several drug families that block viral replication, including nucleoside/nucleotide inhibitors of the HCV RNAdependent RNA polymerase, non-nucleoside inhibitors of the HCV RNA-dependent RNA polymerase, and inhibitors of the NS5A viral protein which plays a regulatory role in replication. Host-targeted agents that inhibit the host cell protein cyclophilin A, a protein required to interact with the replication complex for efficient viral genome production, are also in clinical development. Table 1 summarizes the drugs that have been tested in clinical trials and for which results have been published or presented at medical meetings as of November 2011.

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Cat.No. Product Name Information Publications Customer Product Validation
S1040 Sorafenib Tosylate Sorafenib Tosylate is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM in cell-free assays, respectively. (56) (6)

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