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: A therapeutic window for pharmacological attenuation of HIF activity is demonstrated and the feasibility of disrupting a signal transduction pathway by targeting the function of a transcriptional coactivator with a small molecule is established.
471 citations
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TL;DR: Analysis of PK/PD relationships indicates that the initial hematologic response depends on the administered dose for patients with chronic myeloid leukemia.
Abstract: Purpose To evaluate the basic pharmacokinetic (PK) characteristics of imatinib mesylate and assess the relationship between the PK and pharmacodynamic (PD) properties of the drug. Patients and Methods The PK and PD properties of imatinib were investigated during a phase I trial that included 64 adult patients with Philadelphia chromosome–positive leukemias. Patients received imatinib orally once or twice daily. PK parameters of imatinib, derived from the plasma concentration–time curves, were determined. PD response, defined as the WBC after 1 month of treatment with imatinib, was used to develop an efficacy model. A maximum inhibition–effect model was used to describe the relationship between reduction in WBC and drug exposure parameters. Results Imatinib exposure was dose proportional after oral administration for the dose range of 25 to 1,000 mg. There was a 1.5- to three-fold drug accumulation after repeated once-daily dosing. Mean plasma trough concentration was 0.57 μg/mL (approximately 1 μmol/L) 24...
471 citations
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TL;DR: Nearly 40 percent of newly acquired HSV-2 infections and nearly two thirds of new HSv-1 infections are symptomatic, and among sexually active adults, new genital HSVs type 1 and 2 infections are as common as new oropharyngeal HSV -1 infections.
Abstract: Background Herpes simplex virus (HSV) infections are endemic, but the clinical characteristics of newly acquired HSV type 1 (HSV-1) and HSV type 2 (HSV-2) infections in adults have not been rigorously defined. Methods We monitored 2393 sexually active HSV-2–seronegative persons for clinical and serologic evidence of new HSV infection. Of the participants, 1508 were seropositive for HSV-1 and 885 were seronegative. Charts were reviewed in a blinded manner for classification of those with genitourinary or oropharyngeal symptoms. Charts were also reviewed for all 174 persons with HSV seroconversion. Results The rates of new HSV-1 and HSV-2 infections were 1.6 and 5.1 cases per 100 person-years, respectively. Of the 155 new HSV-2 infections, 57 (37 percent) were symptomatic, 47 of which (82 percent) were correctly diagnosed at presentation. Among the 74 patients given a clinical diagnosis of genital HSV-2 infection during the study, 60 were given a correct diagnosis and 14 were given an incorrect diagnosis, f...
471 citations
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TL;DR: Somatostatins are a family of cyclopeptides that have broad inhibitory effects on the secretion of hormones such as growth hormone, insulin and glucagon as discussed by the authors.
Abstract: Somatostatins — also known as somatotropin-release inhibiting factors (SRIFs) — are a family of cyclopeptides that have broad inhibitory effects on the secretion of hormones such as growth hormone, insulin and glucagon. These effects have formed the basis for the clinical use of SRIF analogues in the treatment of acromegaly and endocrine tumours. The discovery of the five SRIF receptor subtypes in the 1990s further enhanced our understanding of the biological roles of SRIFs, and paved the way for new therapeutic opportunities. Here we review recent advances in SRIF biology, the chemistry of SRIF agonists and antagonists, and the therapeutic potential of such compounds in a wide range of established and novel indications.
470 citations
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TL;DR: The high bactericidal activity of the F0F1 ATP synthase inhibitor R207910 on hypoxic nonreplicating bacteria is described, supporting the potential of this drug candidate for shortening the time of tuberculosis therapy.
Abstract: The persistence of Mycobacterium tuberculosis despite prolonged chemotherapy represents a major obstacle for the control of tuberculosis. The mechanisms used by Mtb to persist in a quiescent state are largely unknown. Chemical genetic and genetic approaches were used here to study the physiology of hypoxic nonreplicating mycobacteria. We found that the intracellular concentration of ATP is five to six times lower in hypoxic nonreplicating Mtb cells compared with aerobic replicating bacteria, making them exquisitely sensitive to any further depletion. We show that de novo ATP synthesis is essential for the viability of hypoxic nonreplicating mycobacteria, requiring the cytoplasmic membrane to be fully energized. In addition, the anaerobic electron transport chain was demonstrated to be necessary for the generation of the protonmotive force. Surprisingly, the alternate ndh-2, but not -1, was shown to be the electron donor to the electron transport chain and to be essential to replenish the [NAD+] pool in hypoxic nonreplicating Mtb. Finally, we describe here the high bactericidal activity of the F0F1 ATP synthase inhibitor R207910 on hypoxic nonreplicating bacteria, supporting the potential of this drug candidate for shortening the time of tuberculosis therapy.
470 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 |