Document Detail

Imatinib mesylate for the treatment of pulmonary arterial hypertension.
MedLine Citation:
PMID:  22074410     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted.
AREAS COVERED: This review delineates the current limitations in the management of PAH and focuses on a novel, anti-proliferative therapeutic concept. It will help readers understand the mechanisms of receptor tyrosine kinase signaling, with a special focus on platelet-derived growth factor (PDGF) receptors and their role in the pathobiology of PAH. Furthermore, it provides a comprehensive summary regarding the rationale, efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate , which potently inhibits the PDGF receptor, as an additional treatment option in PAH.
EXPERT OPINION: PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.
Henrik ten Freyhaus; Daniel Dumitrescu; Eva Berghausen; Marius Vantler; Evren Caglayan; Stephan Rosenkranz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2011-11-11
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  21     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-26     Completed Date:  2012-04-20     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  119-34     Citation Subset:  IM    
Klinik III für Innere Medizin, Center for Molecular Medicine Cologne, Universität zu Köln, Kerpener Str. 62, 50924 Köln, Germany.
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MeSH Terms
Clinical Trials as Topic
Drug Delivery Systems
Hypertension, Pulmonary / drug therapy*,  physiopathology
Muscle, Smooth, Vascular / drug effects,  metabolism
Piperazines / adverse effects,  pharmacology,  therapeutic use*
Protein Kinase Inhibitors / adverse effects,  pharmacology,  therapeutic use*
Pyrimidines / adverse effects,  pharmacology,  therapeutic use*
Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
Time Factors
Treatment Outcome
Reg. No./Substance:
0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; BKJ8M8G5HI/imatinib; EC, Platelet-Derived Growth Factor

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