Institution
Novartis
Company•Basel, Switzerland•
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.
Topics: Alkyl, Population, Alkoxy group, Receptor, Cancer
Papers published on a yearly basis
Papers
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TL;DR: Results from the phase 2 COMBI-MB trial provide evidence of clinical benefit with dabrafenib plus trametinib and support the need for additional research to further improve outcomes in patients with melanoma brain metastases.
Abstract: Summary Background Dabrafenib plus trametinib improves clinical outcomes in BRAF V600 -mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases Here, we report results from the phase 2 COMBI-MB trial Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAF V600 -mutant melanoma brain metastases Methods This ongoing, multicentre, multicohort, open-label, phase 2 study evaluated oral dabrafenib (150 mg twice per day) plus oral trametinib (2 mg once per day) in four patient cohorts with melanoma brain metastases enrolled from 32 hospitals and institutions in Europe, North America, and Australia: (A) BRAF V600E -positive, asymptomatic melanoma brain metastases, with no previous local brain therapy, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (B) BRAF V600E -positive, asymptomatic melanoma brain metastases, with previous local brain therapy, and an ECOG performance status of 0 or 1; (C) BRAF V600D/K/R -positive, asymptomatic melanoma brain metastases, with or without previous local brain therapy, and an ECOG performance status of 0 or 1; and (D) BRAF V600D/E/K/R -positive, symptomatic melanoma brain metastases, with or without previous local brain therapy, and an ECOG performance status of 0, 1, or 2 The primary endpoint was investigator-assessed intracranial response in cohort A in the all-treated-patients population Secondary endpoints included intracranial response in cohorts B, C, and D This study is registered with ClinicalTrialsgov, number NCT02039947 Findings Between Feb 28, 2014, and Aug 5, 2016, 125 patients were enrolled in the study: 76 patients in cohort A; 16 patients in cohort B; 16 patients in cohort C; and 17 patients in cohort D At the data cutoff (Nov 28, 2016) after a median follow-up of 8·5 months (IQR 5·5–14·0), 44 (58%; 95% CI 46–69) of 76 patients in cohort A achieved an intracranial response Intracranial response by investigator assessment was also achieved in nine (56%; 95% CI 30–80) of 16 patients in cohort B, seven (44%; 20–70) of 16 patients in cohort C, and ten (59%; 33–82) of 17 patients in cohort D The most common serious adverse events related to study treatment were pyrexia for dabrafenib (eight [6%] of 125 patients) and decreased ejection fraction (five [4%]) for trametinib The most common grade 3 or worse adverse events, regardless of study drug relationship, were pyrexia (four [3%] of 125) and headache (three [2%]) Interpretation Dabrafenib plus trametinib was active with a manageable safety profile in this melanoma population that was consistent with previous dabrafenib plus trametinib studies in patients with BRAF V600 -mutant melanoma without brain metastases, but the median duration of response was relatively short These results provide evidence of clinical benefit with dabrafenib plus trametinib and support the need for additional research to further improve outcomes in patients with melanoma brain metastases Funding Novartis
487 citations
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TL;DR: This paper showed that SGK3 undergoes PI3K-and PDK1-dependent activation in PIK3CA mutant cancer cells and showed that these cells retain robust PDK 1 activation and membrane localization and exhibit dependency on the SGK 1 substrate SGK 3.
487 citations
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TL;DR: Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease.
486 citations
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TL;DR: The primary endpoint, including incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen, irrespective of aspirin use, suggesting that lumirACoxib is an appropriate treatment for patients with osteoarthritis, who are often at high cardiovascular risk and taking low-dose aspirin.
486 citations
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TL;DR: In this article, the crystal structures of a dengue NS2B-NS3pro complex and a West Nile virus NS2b-NS 3pro complex with a substrate-based inhibitor were reported.
Abstract: The replication of flaviviruses requires the correct processing of their polyprotein by the viral NS3 protease (NS3pro). Essential for the activation of NS3pro is a 47-residue region of NS2B. Here we report the crystal structures of a dengue NS2B-NS3pro complex and a West Nile virus NS2B-NS3pro complex with a substrate-based inhibitor. These structures identify key residues for NS3pro substrate recognition and clarify the mechanism of NS3pro activation.
485 citations
Authors
Showing all 41972 results
Name | H-index | Papers | Citations |
---|---|---|---|
Irving L. Weissman | 201 | 1141 | 172504 |
Peter J. Barnes | 194 | 1530 | 166618 |
Paul G. Richardson | 183 | 1533 | 155912 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Jie Zhang | 178 | 4857 | 221720 |
Lei Jiang | 170 | 2244 | 135205 |
Marc A. Pfeffer | 166 | 765 | 133043 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Bruce D. Walker | 155 | 779 | 86020 |
Timothy P. Hughes | 145 | 831 | 91357 |
Kurt Wüthrich | 143 | 739 | 103253 |
Leonard Guarente | 143 | 352 | 80169 |
Christopher D.M. Fletcher | 138 | 674 | 82484 |