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Trypsin Inhibitors

Is there an overprescription of proton pump inhibitors in oncohematologic patients undergoing ambulatory oncospecific treatment?

... la publicación de sus artículos. 10/8/16 2:43 Is there an overprescription of proton pump inhibitors in oncohematologic... Contribution to scientific literature This study presents data, so far unknown, on the prevalence of prescription of proton pump inhibitors (PPIs) and the level of adequacy of their indication in oncohematologic patients undergoing ... 1):328-9. Raghunath AS, O’Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63. Van Soest EM, Siersema PD, Dieleman JP, Sturkenboom MCJM, Kuipers EJ. Persistence and adherence to proton pump inhibitors in daily clinical practice. Aliment Pharmacol Ther. 2006;24(2):377–85. García del ... Raghunath AS, O’Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63. 3. Van Soest EM, Siersema PD, Dieleman JP, Sturkenboom MCJM, Kuipers EJ. Persistence and adherence to proton pump inhibitors in daily clinical practice. Aliment Pharmacol Ther. 2006;24(2):377–85. 4. García
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Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction.

... hydrophobic residues: Phe19, Trp23, and Leu26. Several inhibitors which target the MDM2-p53 interaction have been published [12]. These inhibitors can be divided into three groups: type I, II and III [13]. Type I inhibitors are peptide oligomers designed to mimic the α-helical topography. Type II inhibitors are based on scaffolds that place substituents ... compounds showed no activity. Re-evaluation of the design was therefore performed, aiming for type II inhibitors. Design of type II inhibitors During our studies with type III inhibitors, new crystal structures of MDM2 co-crystallised with highly potent type II inhibitors were published [15,35–37]. Analysis of these as well as previously published crystal ... design, synthesis, and biological evaluation of 2,5-DKP derivatives as potential MDM2-p53 inhibitors. Results and Discussion Design of type III inhibitors It was anticipated that spiro-DKPs (Fig 2A) would be a suitable starting point for the development of novel type III inhibitors, as these shape-programmable scaffolds can project functional groups into
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Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design.

... directed IN inhibitors. In conclusion, we have studied the LEDGF binding pocket of HIV IN by using a series of synthetic compounds based on initial hits from a fragment based screen and have identified low micromolar inhibitors based on in vitro biochemical, biophysical and cellular assays. These compounds represent new scaffolds for the design of inhibitors ... containing LEDGF were pooled, dialysed against 25 mM Tris-Cl pH 7.0, 0.5 M NaCl, 5 mM DTT, 5% (v/v) making it a tantalizing target for inhibitors [11,14,18,19]. While our study was underway, several groups reported small molecule inhibitors that bind to this site in HIV IN [8,25–28]. One group used a pharmacophore based on the interactions of the residues ... preventing this step can reduce viral replication and viral load. Current IN inhibitors, such as raltegravir (IsentressTM), bind at the catalytic site of IN and resistance is developed rapidly in the clinic even under optimized HAART [42]. We therefore set out to develop small molecule inhibitors of HIV IN that did not target the catalytic site. Our approach
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Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.

... for the cellular efficacy of DYRK1A inhibitors [28]. HeLa cells were transiently transfected with a GFP-SF3B1 expression vector and treated with three of the new β-carbolines (AnnH31, AnnH43, AnnH75) in parallel with three established DYRK1A inhibitors (harmine, L41, INDY). Western blot analysis showed that the new inhibitors reduced the phosphorylation ... β-carbolines were examined for selectivity against kinases that are typical targets of other DYRK1A inhibitors, i.e. DYRK1B, DYRK2, HIPK2 and CLK1. Overall, most compounds showed a similar selectivity profile towards these kinases (Fig 1). The more potent DYRK1A inhibitors also inhibited DYRK1B, although slightly less efficiently than DYRK1A. In contrast ... has been reported to cause mitotic arrest [43]. PLOS ONE | DOI:10.1371/journal.pone.0132453 July 20, 2015 6 / 18 Novel β-Carboline DYRK1A Inhibitors Table 2. Kinome selectivity of AnnH75 and published DYRK1A inhibitors. a Residual activity (% of control) AnnH75 (1 μM) Harmine (1μM) Harmine (10 μM) L41 (10 μM) Leucett-amine B (10 μM) INDY (10
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General amyloid inhibitors? A critical examination of the inhibition of IAPP amyloid formation by inositol stereoisomers.

... and development of islet amyloid inhibitors compared to that invested in studies of Ab inhibitors. Thus, it is natural to inquire if Ab inhibitors are effective against IAPP in light of the features shared by the two polypeptides, and given that amyloid formation by IAPP can be seeded by Ab [20]. None of the existing IAPP inhibitors have been clinically ... conformational change in IAPP and are ineffective inhibitors of IAPP amyloid formation, although some do lead to modest apparent changes in IAPP amyloid fibril morphology. Thus not all classes of Ab inhibitors are effective against IAPP. This work provides a basis of comparison to work on polyphenol based inhibitors of IAPP amyloid formation and helps ... states and share some common characteristics. Comparatively little effort has been expended on the design of IAPP amyloid inhibitors, thus it is natural to inquire if Ab inhibitors are effective against IAPP, especially since no IAPP inhibitors have been clinically approved. A range of compounds inhibit Ab amyloid formation, including various stereoisomers
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Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection.

... manuscript. Competing Interests: The authors have declared that no competing interests exist. The mechanisms of action by which cyclophilin inhibitors (CypI) interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai), but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs), which ... caused PLOS ONE | DOI:10.1371/journal.pone.0159511 July 21, 2016 1 / 17 Membrane Reorganization by Cyclophilin Inhibitors by hepatitis C [3]. Fortunately, several direct-acting antiviral (DAAs) such as NS3 (NS3i), NS5A (NS5Ai) and NS5B (NS5Bi) inhibitors have been FDA-approved and have shown high efficacy in patients, but the cost of these IFN-free DAA ... Cyclophilin inhibitors (CypI) represent the most advanced HTAs in the treatment of HCV-infected patients. The CypI, alisporivir (ALV), provided high efficacy as HTA treatment with or without IFN in phase II and III studies [8–10]. IFN-free ALV treatment is highly effective in GT2 and 3 patients [8]. This is significant since NS3i, NS5Ai and NS5Bi inhibitors
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Elimination of Enhanced Thermal Resistance of Spheroid Culture Model of Prostate Carcinoma Cell Line by Inhibitors of Hsp70 Induction

... culture flasks (Nunc). The cultures were maintained at 37°C in a humidified atmosphere of 7.5% CO2. Cultures were propagated or cells were harvested by trypsinzing cultures with 0.5 mM EDTA/ 0.25% (w/v) trypsin in phosphate buffer saline (PBS). Spheroid culture Spheroids were initiated using the liquid overlay Yakhteh Medical Journal, Vol 12, No 1, Spring ... were treated with 500 μM quercetin and hyperthermia as described for monolayer cultures. They were then treated with 300 μl of PBS containing 1 mM EDTA/0.25% (w/v) trypsin for 10 minutes at 37°C. Trypsin was neutralized by the addition of 700 μl culture medium containing FCS. Half of the spheroids were mechanically disaggregated, and single cells were counted ... Original Article Elimination of Enhanced Thermal Resistance of Spheroid Culture Model of Prostate Carcinoma Cell Line by Inhibitors of Hsp70 Induction Samideh Khoei, Ph.D.1, Gholam Reza Fazeli, M.Sc.2, Atefeh Amerizadeh, M.Sc.2, Delaram Eslimi, M.Sc.3, Bahram Goliaei, Ph.D.2* 1. Medical Physics Department,
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Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

... Risk of Hormone Escape in a Human Prostate Cancer Model Depends on Therapy Modalities and Can Be Reduced by Tyrosine Kinase Inhibitors Charlotte Guyader1, Jocelyn Céraline2, Eléonore Gravier1,3,4,5, Aurélie Morin6, Sandrine Michel7, Eva Erdmann2, Gonzague de Pinieux8, Florence Cabon6, Jean-Pierre ... Céraline J, Gravier E, Morin A, Michel S, et al. (2012) Risk of Hormone Escape in a Human Prostate Cancer Model Depends on Therapy Modalities and Can Be Reduced by Tyrosine Kinase Inhibitors. PLoS ONE 7(8): e42252. doi:10.1371/journal.pone.0042252 Editor: Irina Agoulnik, Florida International University, United States of America Received January 16, 2012; ... AR mutations, and growth factor expression/activation were studied. The involvement of phosphorylation pathways in hormone escape led us to test combination of tyrosine kinase inhibitors with pharmacological castration to reduce the risk of tumor recurrence. RT-PCR mRNA Analysis Total RNA was extracted as previously published [21]. Sequences of primers
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Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb) 2 insights to identify novel inhibitors

... http://svimstpt.ap.nic.in/jcsr/oct-dec16_files/sf.16.07.006.pdf DOI: http://dx.doi.org/10.15380/2277-5706.JCSR.16.07.006 252 Novel inhibitors of Grb2 Sandeep et al Gleevec CEP-701 and P27 were reported as inhibitors of Grb2 which stops its function by blocking association of guanine nucleotide exchange factor SOS.5 Grb2 inhibitors were unclear in preclinical levels and some were under development.5 ... Novel inhibitors of Grb2 Sandeep et al Short Communication: Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb) 2 insights to identify novel inhibitors Sandeep Swargam,1 Hema Kanipakam,1 Natrajan Pradeep,1M.M Suchitra,2J. Rajeswari,3A.Umamaheswari1 ... K, Pradeep N, Suchitra MM, Rajeswari J, Umamaheswari A. Molecular docking and dynamic studies of human growth factor receptor-bound protein (Grb) 2 insights to identify novel inhibitors. J Clin Sci Res 2016;5:252-8. DOI: http://dx.doi.org/10.15380/2277-5706.JCSR.16.07.006. INTRODUCTION Mitogen activated protein kinase (MAPK) pathway plays an important
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Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

... a11111 RESEARCH ARTICLE Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice Marco Redaelli1,2☯, María Jimena Ricatti1,3☯, Marialaura Simonetto1, Mirko Claus1, Maurizio Ballabio4, Antonio Caretta2,5, Carla ... work. * carla.mucignat@unipd.it OPEN ACCESS Citation: Redaelli M, Ricatti MJ, Simonetto M, Claus M, Ballabio M, Caretta A, et al. (2015) Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice. PLoS ONE 10(3): e0121883. doi:10.1371/journal.pone.0121883 Academic Editor: Joseph Charles Glorioso, University of Pittsburgh School ... neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide
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Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study.

... cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 148: 379–397. 5. Panza F, Solfrizzi V, Frisardi V, Capurso C, D’Introno A, et al. (2009) Diseasemodifying approach to the treatment of Alzheimer’s disease: from alphasecretase activators to gamma-secretase inhibitors and ... University of Florence, Florence, Italy, 5 Novartis Farma Italia, Origgio (Varese), Italy Abstract Patients with Alzheimer’s disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another ... different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer’s disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained
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Letter: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database ( 2015;39:247-52)

... with the use of DPP-4 inhibitors led to many systematic reviews and meta-analyses. In addition to many previous studies, the largest meta-analysis study of recent years showed that a long-term treatment with DPP-4 inhibitors significantly increased the risk of HF [5].   Another way of studying the risk of HF associated with DPP4 inhibitors is to analyze ... Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database (Diabetes Metab J 2015;39:247-52) Dae Ho Lee Department of Internal Medicine, Wonkwang University School of Medicine & Hospital, Iksan, Korea Dipeptidyl peptidase-4 (DPP-4) inhibitors are now being widely used for the treatment ... GM. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in diabetic patients: a meta-analysis. Int J Cardiol 2015;181:239-44. 6. Suh S, Seo GH, Jung CH, Kim MK, Jin SM, Hwang YC, Lee BW, Kim JH. Increased risk of hospitalization for heart failure with newly prescribed dipeptidyl peptidase-4 inhibitors and pioglitazone using the Korean Health
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FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors.

... transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk ... e53190 FLT3 Mutated ETP-ALL Figure 2. Effects of tyrosine kinase inhibitors on proliferation in T-ALL cell lines transfected with FLT3 expression constructs (A–C). Fourty-eight hours (hrs) after transfection, cells were seeded and cultured for additionally 48 hrs with tyrosine kinase inhibitors (PKC412, TKI258, and Sorafenib) and chemotherapy (AraC). ... survival. P-value was calculated by the Log-Rank test. (DOC) Figure S4 Effects of tyrosine kinase inhibitors on apoptosis in Jurkat cells transfected with FLT3 expression constructs. Fourty-eight hrs after transfection the cells were cultured with tyrosine kinase inhibitors (A: Sorafenib, B: PKC412, and C: TKI258) or D: AraC. Apoptosis assay was performed
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Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss.

... exposed to protease inhibitors in vivo or in vitro. The upper part of the figure lists cleavage site mutations most often observed in viruses exposed to protease inhibitors in vivo. The cleavage site mutations shown in the lower part of the figure were selected by in vitro passage of laboratory strains of HIV-1 in the presence of protease inhibitors as described ... Summary Protease inhibitors are among the most active antiviral drugs used in the treatment of Human immunodeficiency virus type 1 (HIV-1) infection. The efficacy of these compounds, however, can be threatened by the emergence of viral resistance, the result of the gradual accumulation of specific mutations in the viral protease. HIV-1 resistance to protease inhibitors ... their effect on resistance persists. Citation: Dam E, Quercia R, Glass B, Descamps D, Launay O, et al. (2009) Gag Mutations Strongly Contribute to HIV-1 Resistance to Protease Inhibitors in Highly Drug-Experienced Patients besides Compensating for Fitness Loss. PLoS Pathog 5(3): e1000345. doi:10.1371/journal.ppat.1000345 Editor: Jeremy Luban, University
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New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment

... SHORT REPORT Rec. Nat. Prod. 8:3 (2014) 286-289 New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment Paul Coulerie1, Alexandre Maciuk2, Cécilia Eydoux3, Edouard Hnawia1, ... a glucose in C4’, strongly inhibited the DENV-NS5 RdRp (IC50= 1.9 µM) whereas the additional glucose induced a loss of activity for quercetin-3,4’-di-O-glucoside (9). New inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia 288 1 (3.6 µM) 2 (> 30 µM) 3 (1.7 µM) 4 (2.1 µM) 5 (> 20 µM) 6 (1.7 µM) 7 (9.5 µM) 8 (1.9 ... Guillemot, V. Dumontet, C. Poullain, B. Canard, F. Guéritte and M. Litaudon (2011). Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors, J. Nat. Prod. 74, 2446–2453. [3] P. Coulerie, C. Eydoux, E. Hnawia, L. Stuhl, A. Maciuk, N. Lebouvier, B. Canard, B. Figadère, J-C. Guillemot and M. Nour (2012). Biflavonoids
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Molecular characterization of c-Abl/c-Src kinase inhibitors targeted against murine tumour progenitor cells that express stem cell markers.

... imatinib’s chemoresistance, dual kinase inhibitors against c-Abl and c-Src were developed and dasatinib (Sprycel) is the first generation of a new class of dual kinase inhibitors displaying striking therapeutic benefit [8,9]. PLoS ONE | www.plosone.org 1 November 2010 | Volume 5 | Issue 11 | e14143 c-Abl/c-Src Inhibitors Specifically, dasatinib ... with the tyrosine kinase inhibitors sorafenib (Nexavar) or sunitinib (Sutent) demonstrate the therapeutic value of multikinase inhibition [17–20]. Taken collectively, there is considerable evidence for c-Src and c-Abl dual kinase inhibitors to represent an important strategy in the combat of cancer. The design of novel c-Abl/c-Src inhibitors on the basis ... effects of a series of dual kinase inhibitors on growth and resistance of tumours and to identify possible candidates for further preclinical development. c-Abl/c-Src dual kinase inhibitors As the 17 4-amino-substituted pyrazolo[3,4-d]pyrimidine deriv- atives 4–5 and 9–23 were ATP-competitive, the dual kinase inhibitors were tested for kinase inhibition
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Condensed tannins from Ficus virens as tyrosinase inhibitors: structure, inhibitory activity and molecular mechanism.

... with Parkinson’s disease and other neurodegenerative diseases [8,9]. Therefore, tyrosinase inhibitors are quite significant in the area of cosmetic and medicinal industry, typically in the cosmetic industry where the development and screening of potent tyrosinase inhibitors are especially attractive. Condensed tannins have received considerable attention ... dodecamer, and pentadecamer, respectively. Antityrosinase activities of the condensed tannins were studied. The results indicated that the condensed tannins were potent tyrosinase inhibitors. The concentrations for the leaves, fruit, and stem bark condensed tannins leading to 50% enzyme activity were determined to be 131.67, 99.89, and 106.22 mg/ml on monophenolase ... type, and constants of the condensed tannins on the diphenolase activity were further investigated. The results indicated that the condensed tannins were reversible and mixed type inhibitors. Fluorescence quenching, copper interacting, and molecular docking techniques were utilized to unravel the molecular mechanisms of the inhibition. The results showed
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Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells.

... oHSV replication compared to inhibitors that selectively target class II HDACs. These studies demonstrate that select HDAC inhibitors increase oHSV replication in breast cancer cells and provides support for preclinical evaluation of this combination strategy. Citation: Cody JJ, Markert JM, Hurst DR (2014) Histone Deacetylase Inhibitors Improve the Replication ... in a limited number of studies that HDAC inhibitors may have the ability to improve oHSV virotherapy [11–13]. In this report, we screened a panel of HDAC inhibitors comprising several different chemical classes for their potential to augment the replication of oHSV in breast cancer cells. Because many of these inhibitors have not been tested in the cell ... March 2014 | Volume 9 | Issue 3 | e92919 HDAC Inhibitors Enhance oHSV Replication Viral replication was assessed by pre- and co-treatment with the HDAC inhibitors at concentrations greater than, less than, and near their LD50 and at both high and low multiplicity of infection (MOI). Select HDAC inhibitors improved oHSV replication in the cancer
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