Vertex Pharmaceuticals

About: Vertex Pharmaceuticals is a company organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Ivacaftor & Hepatitis C virus. The organization has 2135 authors who have published 2022 publications receiving 134750 citations. The organization is also known as: Vertex Pharmaceuticals Inc. & Vertex.

Combination of a Hepatitis C Virus NS3-NS4A Protease Inhibitor and Alpha Interferon Synergistically Inhibits Viral RNA Replication and Facilitates Viral RNA Clearance in Replicon Cells

Abstract: The present standard of care for hepatitis C virus (HCV) infection is pegylated alpha interferon (IFN-α) in combination with ribavirin. However, specific antivirals such as HCV NS3-NS4A protease inhibitors are now in clinical development, and these agents can potentially be used in combination with the present treatments. Therefore, it is important to investigate the potential benefits or adverse effects of these new combinations by using available in vitro HCV culture systems first. In the present study we demonstrate that the combination of a specific HCV NS3-NS4A protease inhibitor and IFN-α synergistically inhibits HCV RNA replication in replicon cells, with little or no increase in cytotoxicity. Furthermore, the benefit of the combination was sustained over time, such that a greater than 3-log reduction in HCV RNA levels was achieved following 9 days of treatment. The viral RNA appeared to be cleared from the replicon cells after 14 days of treatment, and no viral RNA rebound was observed upon withdrawal of the inhibitors. In each case, the antiviral effects obtained with higher concentrations of either the protease inhibitor alone or IFN-α alone can be achieved by a combination of both agents at lower concentrations, which may potentially reduce the risk of possible adverse effects associated with high doses of either agent.

Pyridyl derivatives as cftr modulators

Abstract: The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Drug discovery effectiveness from the standpoint of therapeutic mechanisms and indications.

Abstract: The productivity of the pharmaceutical industry has been widely discussed in recent years, particularly with regard to concerns that substantial expenditures on research and development have failed to translate into approved drugs. Various analyses of this productivity challenge have focused on aspects such as attrition rates at particular clinical phases or the physicochemical properties of drug candidates, but relatively little attention has been paid to how the industry has performed from the standpoint of the choice of therapeutic mechanisms and their intended indications. This article examines what the pharmaceutical industry has achieved in this respect by analysing comprehensive industry-wide data on the mechanism-indication pairs that have been investigated during the past 20 years. Our findings indicate several points and trends that we hope will be useful in understanding and improving the productivity of the industry, including areas in which the industry has had substantial success or failure and the relative extent of novelty in completed and ongoing projects.

Compounds and methods for the treatment or prevention of flavivirus infections

Abstract: A compound is represented by Structural Formula (I), or a pharmaceutically acceptable salt thereof, wherein the variables of Structural Formula (I) are as described in the specification and the claims. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier of excipient. A method of treating a HCV infection in a subject comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of inhibiting or reducing the activity of HCV polymerase in a subject or in a biological in vitro sample comprises administering to the subject or to the sample a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof.