Fred De Clerck
Affiliation: Johnson and Johnson Pharmaceutical Research and Development
- In vitro effects of risperidone and 9-hydroxy-risperidone on human platelet function, plasma coagulation, and fibrinolysisFred De Clerck
Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium
Clin Ther 26:1261-73. 2004..Thrombotic events have been reported with the use of antipsychotic compounds, although the incidence, predisposing factors, and biological mechanisms associated with these events in psychiatric patients are subject to debate...
- Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitorsJ Ignacio Andrés
Janssen Cilag, Basic Research Centre, Jarama s n, 45007, Toledo, Spain
Bioorg Med Chem Lett 12:653-8. 2002..Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration...
- In vivo measurement of QT prolongation, dispersion and arrhythmogenesis: application to the preclinical cardiovascular safety pharmacology of a new chemical entityFred De Clerck
Center of Excellence for Cardiovascular Safety Research, Janssen Research Foundation, Turnhoutseweg 30, B 2340 Beerse, Belgium
Fundam Clin Pharmacol 16:125-40. 2002..Appropriate tests in experimental animals play a key role in this process...
- Drug-induced long QT in isolated rabbit Purkinje fibers: importance of action potential duration, triangulation and early afterdepolarizationsHua Rong Lu
Center of Excellence for Cardiovascular Safety Research, Johnson and Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B 2340 Beerse, Belgium
Eur J Pharmacol 452:183-92. 2002....
- Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in miceRobert Ten Broeke
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80 082, 3508 TB Utrecht, The Netherlands
Respir Res 7:58. 2006..The exact role of the endothelial NOS (eNOS) isoform in asthma is still unknown. We hypothezised that a delicate regulation in the production of NO and its bioactive forms by eNOS might be the key to the pathogenesis of asthma...
- In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine)Paul A J Janssen
Center for Molecular Design, Janssen Pharmaceutica, B-2350 Vosselaar, Belgium
J Med Chem 48:1901-9. 2005..The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others...
- Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugsJean-Pierre Valentin
Safety Assessment UK, AstraZeneca, Mereside Alderley Park, Macclessfield, Cheshire, England, UK
J Pharmacol Toxicol Methods 49:171-81. 2004..In combination with other in vitro and in vivo repolarization assays and with pharmacokinetic data in man, it is a valuable tool to establish an integrated cardiovascular risk assessment of pharmaceutical compounds...
- Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophagesRobert Ten Broeke
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Lab Invest 84:29-40. 2004..These results may contribute to new therapeutic strategies against oxidative stress in airway diseases...
- Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthmaRobert Ten Broeke
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
Eur J Pharmacol 476:151-7. 2003..Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma...
- Detection of proarrhythmia in the female rabbit heart: blinded validationLuc M Hondeghem
Department of Pharmacology, K U Leuven, Leuven, Belgium
J Cardiovasc Electrophysiol 14:287-94. 2003..Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study...
- Differential responsiveness of proximal and distal parts of isolated guinea pig tracheaJoris Kloek
Department of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
Eur J Pharmacol 442:289-94. 2002..In conclusion, the higher intrinsic contractility of proximal tracheal segments is counteracted by serosal cyclo-oxygenase products...
- Short patent lives jeopardize drug and patient safetyLuc M Hondeghem
Department of Pharmacology, Catholic University of Leuven, Belgium
J Cardiovasc Pharmacol 50:353-7. 2007..Therefore, we suggest that the potential benefits of patent life prolongation should be considered, under certain conditions for the sake of patient safety...