Vince Russell

Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases

Elisabetta Armani, Carmelida Capaldi, Valentina Bagnacani, Francesca Saccani et autres

The identification of novel inhaled p38α/β mitogen-activated protein kinases (MAPK) (MAPK14/11) inhibitors suitable for the treatment of pulmonary inflammatory conditions has been described. A rational drug design approach started from the identification of a novel tetrahydronaphthalene series, characterized by nanomolar inhibition of …

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Quantitation of hydroxyproline in a mouse model of bleomycin-induced lung fibrosis: comparison with histological analysis

Viola Bigatto, Elena Manni, Daniela Pompilio, Mariapia Brana’ et autres

Biochemical evaluation of collagen content by hydroxyproline assay is one of the standard endpoints in the preclinical assessment of therapeutics for IPF. The presence of many steps in the hydroxyproline assay workflow could contribute to low assay reproducibility and impact on the …

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Inhaled calcium salts inhibit tobacco smoke-induced inflammation by modulating expression of chemokines and cytokines

Paulette W. Andreotta, Steve Arold, Jennifer A. Kenyon, Paul Woodman et autres

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Steroid-resistant inflammation in a mouse model of severe asthma is not inhibited by the combination of theophylline and budesonide

Vince Russell, Mariapia Brana’, Daniela Pompilio, Giulia Ambrosi et autres

Introduction: Severe asthma patients have a neutrophilic airway inflammation poorly controlled by steroids. This feature of the disease is similar to the steroid-resistant neutrophilic inflammation associated with COPD. It has previously been shown in a mouse model of COPD that Theophylline, in …

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The Effect of the CXCR1/2 Antagonist SCH257123 in a Mouse Model of Severe Asthma

Alan Young, Puneeta Nath, Emma Sadler, Kevin Thang et autres

Objective Severe asthma patient phenotypes are characterised as hard to control by low dose inhaled corticosteroids (ICS) and patients often require high doses of oral steroids for optimum symptom control. There is a high unmet medical need for novel therapies for the …

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The effects of clinically relevant reference agents in a mouse model of severe asthma

Puneeta Nath, Emma Sadler, Vince Russell, Alan Young

Severe asthma is not controlled by normal doses of inhaled or oral corticosteroids. Patients need high dose oral steroids and there is an unmet medical need for new therapies. Neutrophilic airway inflammation, mediated by Th17 cytokines, has been associated with corticosteroid insensitivity …

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Pharmacological profile and efficacy of GLPG1690, a novel ATX inhibitor for COPD treatment

Roland Blanqué, Nicolas Desroy, Sonia Dupont, Céline Cottereaux et autres

Introduction: Autotaxin (ATX), a secreted lysophospholipase, plays a central role in the production of the bioactive lipid lysophosphatidic acid (LPA). LPA signals through multiple LPA receptors to control a range of cell activities (migration, contraction, survival…). Recently, a role for the ATX/LPA …

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Initial Characterization of A Mouse Model of Severe Asthma

Alan A. Young, Emma Sadler, Puneeta Nath, Vince Russell

Severe asthma patients have symptoms that are frequently hard to manage with low dose inhaled corticosteroids (ICS) and often need additional high dose oral steroids. Neutrophilic airway inflammation is also associated with corticosteroid insensitivity in this population. We have investigated the effect …

The Effect of Stimulatory Compounds on Baseline and Impaired Mucociliary Clearance in the Guinea Pig

Alan G. Young, Emma Sadler, Puneeta Nath, Vince Russell

Mucociliary clearance (MCC) is an important mechanism for clearing the lung of foreign matter and is impaired in diseases such as COPD. Smoking reduces MCC in humans and may contribute to the disease, whereas agents such as β2-adrenergic agonists, hypertonic saline and …

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Characterisation of a steroid-insensitive severe asthma model

Puneeta Nath, Alan Young, Vince Russell

Approximately 10% of asthmatics can be classified as having severe asthma. Inhaled steroids are often ineffective in these patients and they are often characterised as having neutrophilic lung inflammation. Here we report on the development of a pre-clinical severe asthma model characterised …

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The design of a novel series of muscarinic receptor antagonists leading to AZD8683, a potential inhaled treatment for COPD

Antonio Mete, Keith C. Bowers, Richard J. Bull, Helen Coope et autres

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The effects of intra-nasally administered anti-inflammatory compounds in a mouse model of acute COPD exacerbations

Vince Russell, Andrew J. Connolly, Joanna Dlugozima, Paul Woodman et autres

Exposure to tobacco smoke (TS) for 4d induced a steroid-insensitive lung inflammation in mice which was exaggerated by the addition of the viral mimetic poly IC (pIC). The effects of an inhaled steroid and an inhaled p38 inhibitor on the exaggerated inflammation …