Institution
Vertex Pharmaceuticals
Company•Boston, Massachusetts, United States•
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.
Topics: Ivacaftor, Hepatitis C virus, Protease, Telaprevir, Protein kinase A
Papers published on a yearly basis
Papers
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TL;DR: An overview of recent results in these areas can be found in this paper, where a considerable number of publications have appeared that focus on the enantioselective addition of acetylenes to carbonyls and imines.
257 citations
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TL;DR: In vitro pharmacology of a high potency, selective VR1 antagonist that, unlike capsazepine, has potent blocking effects on low pH-induced activation of rat VR1 is described, making it a more suitable candidate for testing the role played by VR1 in rat models of human disease.
Abstract: Vanilloids such as capsaicin have algesic properties and seem to mediate their effects via activation of the vanilloid receptor 1 (VR1), a ligand-gated ion channel highly expressed on primary nociceptors. Although blockade of capsaicin-induced VR1 activation has been demonstrated in vitro and in vivo with the antagonist capsazepine, efficacy in rat models of chronic pain has not been observed with this compound. Here, we describe the in vitro pharmacology of a highly potent VR1 antagonist, N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC). Similar to capsazepine, this compound inhibits capsaicin-induced activation of rat VR1 with an IC50 value of 35 nM. Interestingly however, BCTC also potently inhibits acid-induced activation of rat VR1 (IC50 value of 6.0 nM), whereas capsazepine is inactive. Similarly, in the rat skin-nerve preparation both BCTC and capsazepine block capsaicin-induced activation, whereas the response to acidification is inhibited by BCTC, but not by capsazepine. Specificity for VR1 was demonstrated against 63 other receptor, enzyme, transporter, and ion channel targets. BCTC was orally bioavailable in the rat, demonstrating a plasma half-life of approximately 1 h and significant penetration into the central nervous system. Thus, BCTC is a high potency, selective VR1 antagonist that, unlike capsazepine, has potent blocking effects on low pH-induced activation of rat VR1. These properties make it a more suitable candidate than capsazepine for testing the role played by VR1 in rat models of human disease.
256 citations
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TL;DR: Ten weeks after starting off‐study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa‐2a group, and 1 patient in the placebo
256 citations
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TL;DR: Telaprevir increased the blood concentrations of both cyclosporine and tacrolimus significantly, which could lead to serious or life‐threatening adverse events, and its use in organ transplant patients is not recommended.
253 citations
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TL;DR: The crystal structure of the apo, unphosphorylated form of p38 kinase has been solved at 2.3 Å resolution and the relative orientation of the two domains of p 38 kinase is different from that observed in the active form of cAMP-dependent protein kinase.
253 citations
Authors
Showing all 2137 results
Name | H-index | Papers | Citations |
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David Altshuler | 162 | 345 | 201782 |
Richard J. Johnson | 137 | 880 | 72201 |
Gerhard Wagner | 116 | 589 | 50309 |
Paul I.W. de Bakker | 107 | 257 | 95323 |
Peter R. Mueller | 97 | 613 | 34457 |
Annamaria Vezzani | 85 | 285 | 26008 |
Mark D. Fleming | 81 | 433 | 36107 |
Santosh Kumar | 80 | 1196 | 29391 |
Thomas Helleday | 76 | 303 | 27757 |
Nicola J. Curtin | 68 | 228 | 18255 |
Susan J. Little | 62 | 276 | 17986 |
Jeremy S. Duffield | 58 | 124 | 16037 |
Edmund V. Capparelli | 54 | 281 | 10747 |
Roy A. Black | 54 | 99 | 16878 |
Murcko Mark A | 53 | 130 | 14347 |