Query : Inhibiteurs
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Dream and schizophrenia: A single neurobiological medium?
Normal waking mentation is the outcome of the combined action of both electrophysiological and neurochemical antagonistic and complementary activating and inhibitory influences occurring mainly in the cerebral cortex. The chemical ones are supported principally by acetylcholine, and noradrenaline an...
Structural characterization of Plasmodium falciparum CTP : phosphocholine cytidylyltransferase and fragment-based drug design approach for targeting phospholipid biosynthesis pathway
Malaria remains a major global health problem and the most threatening parasitic disease. Among the 5 malaria species that affect humans, Plasmodium falciparum is the most deadly form. During its life cycle, in erythrocytic stage, which causes all the malaria symptoms, P. falciparum relies on phosph...
Research on Performance Evaluation and Anti-scaling Mechanism of Green Scale Inhibitors by Static and Dynamic Methods
Increasing environmental concerns and discharge limitations have imposed additional challenges in treating process waters. Thus, the concept of "Green Chemistry" was proposed and green scale inhibitors became a focus of water treatment technology. Finding some economical and environmentally friendly...
Histone deacetylase inhibitors impair antibacterial defenses of macrophages
Les déacetylases d'histones (HDACs) déacétylent non seulement les histones, ce qui a généralement pour effet d'augmenter la transcription et l'expression génique, mais également d'autres protéines comme par exemple des protéines de choc thermique (HSP90), la tubuline alpha, certains récepteurs aux s...
Acquisitions thérapeutiques 2002 : Rhumatologie
De nouveaux dérivés de la classe des coxibes vont faire leur apparition sur le marché. Outre leur action anti- nflammatoire, les coxibes possèdent des propriétés analgésiques. Des études récentes sur de grandes séries de patients ayant reçu du rofécoxibe ne semblent pas démontrer de risques cardiova...
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Immuno editing in myeloid pathology
B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1 participates in the immunoescape of cancer cells and is also involved in the long-term persistence of leukemic cells in a mouse model. B7-H1 can be constitutively expressed by cancer cells but is also induced by various stim...
Implication of CXCR3 in tumor progression : a new therapeutical target
CXCR3 belongs to the G-protein-coupled receptors family. With its ligands, the CXC chemokines, CXCR3 regulates several biological functions and plays important roles in angiogenesis, inflammation and cancer. The interaction with CXCR3 is rather complex due to the presence of distinct spliced isoform...
Palladium-catalyzed synthesis of 5-azaindoles and evaluation of their inhibitory activity on CK2 and Pim-1 kinases
Protein kinases represent promising targets for anti-cancer drug design. In 2003, inhibitors of two of these enzymes, CK2 and Pim-1, were identified by the screening of the Curie Institute/CNRS small-molecule library. The aim of this thesis was to synthesize derivatives of these hits with a 5-azaind...
Epithelial-to-mesenchymal transition in gastric cells : role of Helicobacter pylori-regulated microRNA
MicroRNA are small noncoding RNA that post-transcriptionally regulate gene expression. Due to their high regulator potential, a change in their expression may lead to the emergence of diseases such as cancer or inhibition of defense mechanisms against pathogens. Our aim is to characterize the role o...
Modulation of the expression and function of dopaminergic presynaptic proteins by the statins : Potential implication for the therapeutic intervention in Parkinson’s disease.
Parkinson disease (PD) is characterized by a progressive loss of dopaminergic presynaptic terminals and remains incurable. However in epidemiological studies, it has been shown that the use of statins, which are hypocholesterolemic drugs, diminishes the risk to develop a PD. Statins are able to inhi...
Design, synthesis and pharmacological evaluation of nitrogen heterocycles as anticancer drugs
According to the International Agency for Research on Cancer, cancer is the first cause of death in France with about 150 000 deaths estimated in 2012. This disease is characterized by anarchistic and uncontrolled proliferation of cells that escape control mechanisms. Currently, the anticancer drugs...
Intrabodies targeting conformational organization of the HIV-1 reverse transcriptase as potent new HIV inhibitors.
The rapid emergence of drug-resistant viruses against all approved HIV clinical drugs together with inaccessible latent virus reservoirs and side effects of currently used compounds have limited the potency of existing anti-HIV-1 therapeutics. Therefore, there is a critical need for new safer drugs,...
Resistance to potato Y-virus (PVY) in transgenic potato lines expressing a cystein-like protease inhibitor
La résistance au PVY chez des lignées transgéniques exprimant un inhibiteur de protéase est due en partie à des changements physiologiques occasionnés par l'inhibiteur recombinant exprimé dans la plante. Après clonage et expression hétérologue des protéases de maturation du PVY, nous avons étudié le...
Inhibiting processes in Alzheimer’s disease and fronto-temporal dementia
Statins in cardiovascular therapy
Statins lower circulating cholesterol by blocking the activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. However, statins possess pleiotropic properties that complement their cholesterol lowering effect, and makes this class of drugs very efficient to prevent, stabiliz...
Chemical Ligation Synthesis of extracellular inhibitors of HGF/SF-MET signalling pathway
Use of peptides as biomolecules have been extensively applied to various therapeutic fields (cancer, diabetes, AIDS). The challenge for chemists consists in development of new reliable and efficient strategies. Our work especially focused on the conception of two innovative non native chemical ligat...
Development of Novel Therapeutic Stratégies to Combat Emerging Pathogenic Viruses
Les virus pathogènes émergents sont responsables de maladies parmi les plus sévères et représentent un problème majeur de santé publique. Les arénavirus et les hantavirus sont des virus enveloppés possédant un génome à ARN monocaténaire négatif et sont considérés comme des agents pathogènes d'import...
Anti-inflammatory drugs : an old class innovative treatment of traumatic brain ?
Because of its complex pathology, Traumatic Brain Injury (TBI) leads to numerous cerebral lesions for which there is no neuroprotective treatment. It is clearly known nowadays that neuro-inflammation is highly involved in post-traumatic consequences. This devastating process is manifested among othe...
Dynamics of complex networks, modeling and simulations : application to visual cortex
The aim of this work is to analyze theoretically and numerically the dynamics of a network of excitatory and inhibitory neurons of ordinary differential equations (ODE) of Hodgkin-Huxley type (HH) inspired by the primary visual cortex V1. The model emphasizes an approach combining a driven stochasti...
Characterization of the antiviral activity of 4-aminoquinoline derivatives on the Hepatitis C Virus
Hepatitis C virus (HCV) is a major cause of chronic liver disease for which standard-of-care treatment consisted in a bi-therapy based on two non-specific inhibitors : pegylated interferon-α (IFN-α) and ribavirin. Since 2011 protease inhibitors (boceprevir and telaprevir) increased the response to t...
Developmental and post-leesian plastics of the co-carriers cation-chloride KCC2 and NKCC1 in the spinal cord
Le GABA et la glycine, principaux neurotransmetteurs inhibiteurs de la moelle épinière adulte, jouent un rôle clé dans la plasticité neuronale. Ils peuvent être excitateurs selon la concentration en chlorure du neurone cible. Celle-ci est principalement régulée par les co-transporteurs, KCC2, spécif...
Pharmacochemistry of new inhibitors against rhinovirus infections
Rhinovirus (RV), virus of Picornaviridae family, is known to be the aetiology of more than half of the common cold. Through advances in molecular biology, the rhinoviruses have been associated with much more serious respiratory pathologies (asthma, chronic obstructive pulmonary disease (COPD) and cy...
GABAergic signaling in cortical feedback to the olfactory bulb
Cortical feedback conducts information towards earlier relays of information processing. It is instrumental for sensory perception. In the olfactory system, odorants are never experienced in isolation by the nose, and they might be meaningful to the animal or not depending on the context. Feedback i...
Schizophrenia and cannabinoids: Clinical, experimental and biological data
In the ongoing debate regarding the legal status of cannabis, much emphasis has been put on the consequences of this psychoactive substance. Much less attention has been paid, however, to the very nature of cannabis intoxication. Interestingly, following a close review of the literature, it appears...
Identification of the signaling events associated with FLT3-ITD mutant receptor-induced constitutive proliferation in myeloid cells
The FLT3 receptor is involved in stem cells and myeloid progenitors self renewal processes. In about 30% of the acute myeloid leukemia cases, this receptor is mutated and constitutively active, the most common mutation being duplication of sequences in the juxtamembrane domain (Internal Tandem Dupli...