Institution
Incyte
Company•Wilmington, Delaware, United States•
About: Incyte is a company organization based out in Wilmington, Delaware, United States. It is known for research contribution in the topics: Expression vector & Ruxolitinib. The organization has 1262 authors who have published 1875 publications receiving 75015 citations. The organization is also known as: Incyte Corporation & Incyte Inc..
Topics: Expression vector, Ruxolitinib, Cancer, Polynucleotide, Antibody
Papers published on a yearly basis
Papers
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12 Dec 2006TL;DR: In this article, the authors presented hetero-aryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted polypyrrole[2.3]-pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of JKs.
Abstract: The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
230 citations
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TL;DR: It is demonstrated that JAK-STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and thatJAK inhibition in both populations is required for therapeutic efficacy, providing novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic efficacy in MPNs.
Abstract: The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis (MF) and improves overall survival; however the mechanism by which JAK inhibitors achieve efficacy has not been delineated. MPN patients present with increased levels of circulating pro-inflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single cell profiling demonstrated that hematopoietic cells from MF models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. By contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and non-malignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations.
229 citations
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TL;DR: It is argued that B PI neutralizes the toxic effects of LPS in vivo, and that BPI may represent a new therapeutic approach to the treatment of endotoxic shock.
Abstract: Systemic release of endotoxin (LPS) after Gram-negative infection initiates a cascade of host cytokines that are thought to be the direct cause of shock, multisystem organ failure, and death. Endogenous LPS-binding proteins may play a role in regulating LPS toxicity in vivo. The human neutrophil granule protein bactericidal/permeability-increasing protein (BPI) shares sequence homology and immunocrossreactivity with an acute phase lipopolysaccharide binding protein (LBP) which has been shown to bind to LPS and accelerate LPS activation of neutrophils and macrophages. Although structurally similar, LBP and BPI are apparently functionally antagonistic. We previously showed that BPI inhibits LPS-mediated neutrophil activation in vitro. Here we demonstrate that BPI binds to LPS near the lipid A domain, and formation of the LPS-BPI complex abrogates detrimental host responses to LPS. For example, BPI blocks LPS-stimulated TNF release in vitro and in vivo, and LPS complexed to BPI is not pyrogenic in rabbits. Results demonstrating that BPI is released by stimulated human neutrophils further support the idea that BPI functions extracellularly in vivo to neutralize endotoxin. Taken together, these data argue that BPI neutralizes the toxic effects of LPS in vivo, and that BPI may represent a new therapeutic approach to the treatment of endotoxic shock.
229 citations
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TL;DR: Baricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease and was well tolerated with no unexpected safety findings through week 24.
Abstract: Objectives To investigate baricitinib (LY3009104, formerly INCB028050), a novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate. Methods In this phase IIb study, 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for an additional 12 weeks. Patients assigned to placebo or 1 mg baricitinib were reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 12–24. The primary endpoint was the proportion of patients in the combined 4 and 8 mg groups achieving an American College of Rheumatology 20% (ACR20) response versus placebo at week 12. Results Significantly more patients in the combined baricitinib 4 and 8 mg groups compared with placebo achieved an ACR20 response at week 12 (76% vs 41%, p Conclusions Baricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease. Baricitinib was well tolerated with no unexpected safety findings through week 24. Trial registration number NCT01185353.
222 citations
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15 Mar 1999TL;DR: In this article, an end-labeled target nucleic acid is contacted with an array of probe molecules stably associated with the surface of a solid support under hybridization conditions sufficient to produce a hybridization pattern.
Abstract: Methods are provided for quantitative gene expression analysis. In the subject methods, end-labeled target nucleic acid is contacted with an array of probe molecules stably associated with the surface of a solid support under hybridization conditions sufficient to produce a hybridization pattern. The resultant hybridization pattern can be used to obtain a quantitative information about the genetic profile of the end-labeled target nucleic acid sample, as well as the physiological source from which it is derived. As such, the subject methods find use in a variety of applications.
220 citations
Authors
Showing all 1267 results
Name | H-index | Papers | Citations |
---|---|---|---|
Patrick O. Brown | 183 | 755 | 200985 |
David Botstein | 165 | 468 | 212787 |
Inês Barroso | 113 | 301 | 76241 |
Alessandro M. Vannucchi | 94 | 715 | 35482 |
Ana M. Valdes | 84 | 334 | 26627 |
Mark C. Genovese | 79 | 364 | 26945 |
Michael B. Eisen | 71 | 170 | 89150 |
Jingyue Ju | 61 | 169 | 18952 |
Jeanne F. Loring | 60 | 177 | 14503 |
James Z. Wang | 57 | 225 | 21890 |
Emmett V. Schmidt | 50 | 150 | 9304 |
Günther Sperk | 50 | 124 | 10246 |
Robert C. Newton | 44 | 111 | 7369 |
Magnus Pfahl | 44 | 87 | 8064 |
William V. Williams | 44 | 168 | 7278 |