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: The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA and change in these measures over time does not appear to add to predictive accuracy over baseline levels.
Abstract: Objective. Patients with rheumatoid arthritis (RA) are at increased risk of death. Modern RA therapy has been shown to improve health status, but the relationship of such improvements to mortality risk is unknown. We assessed the relationship between health status and all-cause mortality in patients with RA, using the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study Short Form-36 questionnaire (SF-36) physical and mental component summary scores (PCS, MCS). Methods. Subjects (n = 10,319) were selected from the National Data Bank for Rheumatic Diseases, a prospective longitudinal observational US study with semiannual assessments of HAQ, PCS, and MCS. Risk of death up to 7 years through 2006 was obtained from the US National Death Index. Relationship of HAQ, PCS, and MCS to mortality was assessed using Cox regression models; prediction accuracy was compared using Harrell’s concordance coefficient (C). Results. Over 64,888 patient-years of followup, there were 1317 deaths. Poorer baseline health status was associated with greater mortality risk. Adjusting for age, sex, and baseline PCS and MCS, declines in PCS and HAQ were associated with higher risk of death. HAQ improvement was associated with reduced mortality risk from 6 months through 3 years; a similar relationship was not observed for PCS or MCS improvement. Controlling for baseline values, change in PCS or HAQ did not improve prediction accuracy. Conclusion. The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA. Change in these measures over time does not appear to add to predictive accuracy over baseline levels.
57 citations
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TL;DR: A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was developed from a low molecular weight, highly ligand efficient screening hit, while maintaining the high ligand efficiency of the screening hit.
57 citations
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TL;DR: Defects in HRR and BER and high DNA-PKcs expression, that are common in cancer, confer sensitivity to ATR inhibitor monotherapy and may be developed as predictive biomarkers for personalised medicine.
Abstract: ATR is an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. Cancer-specific defects in the DNA damage response (DDR) may render cancer cells vulnerable to ATR inhibition alone. We determined the cytotoxicity of the ATR inhibitor VE-821 in isogenically matched cells with DDR imbalance. Cell cycle arrest, DNA damage accumulation and repair were determined following VE-821 exposure. Defects in homologous recombination repair (HRR: ATM, BRCA2 and XRCC3) and base excision repair (BER: XRCC1) conferred sensitivity to VE-821. Surprisingly, the loss of different components of the trimeric non-homologous end-joining (NHEJ) protein DNA-PK had opposing effects. Loss of the DNA-binding component, Ku80, caused hypersensitivity to VE-821, but loss of its partner catalytic subunit, DNA-PKcs, did not. Unexpectedly, VE-821 was particularly cytotoxic to human and hamster cells expressing high levels of DNA-PKcs. High DNA-PKcs was associated with replicative stress and activation of the DDR. VE-821 suppressed HRR, determined by RAD51 focus formation, to a greater extent in cells with high DNA-PKcs. Defects in HRR and BER and high DNA-PKcs expression, that are common in cancer, confer sensitivity to ATR inhibitor monotherapy and may be developed as predictive biomarkers for personalised medicine.
57 citations
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TL;DR: Results strongly suggest that the B subunit-binding domain is required for calcineurin activity intracellularly and interacts with the FKBP12-FK506 complex.
57 citations
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06 Aug 2004TL;DR: In this paper, the authors present an invention related to inhibitors of protein kinases and provide pharmaceutical compositions comprising the compounds of the invention, processes for preparing the compounds and methods of using the compositions in the treatment of various disorders.
Abstract: The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention, processes for preparing the compounds and methods of using the compositions in the treatment of various disorders.
57 citations
Authors
Showing all 2137 results
Name | H-index | Papers | Citations |
---|---|---|---|
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 |