Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective

Author(s): Bhuvaneshwar Vaidya *, Ruaab Patel , Aaron Muth , Vivek Gupta*.

Journal Name: Current Medicinal Chemistry

Volume 24 , Issue 22 , 2017

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Abstract:

Background: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is caused by excessive lung scarring. IPF-associated severe mortality can be attributed to late diagnosis due to its generic symptoms, and more importantly due to the lack of effective therapies available. Despite extensive research in the past decades, lung transplant still remains the most effective treatment for IPF. Though two drugs recently approved by FDA, Pirfenidone and Nintedanib, have shown an ability to reduce the progression of disease. However, they have shown minimal survival benefits to patients.

Methods: IPF is a multifaceted disorder with poorly understood pathophysiology. We believe that there are better therapeutic targets veiled in IPF pathophysiology, exploitation of which may improve current therapeutic approaches to the disease. We have performed an extensive literature search using several bibliographic databases for peer reviewed articles discussing molecular targets/pathways involved in the pathogenesis of the disease. Furthermore, studies involving exploitation of these therapeutic targets and potential therapeutic agents were identified.

Results: Recently, new and promising targets have been revealed from GWA studies and genetic microarrays of IPF patients. In this review, we discuss the efficacy and feasibility of several novel molecular targets including Semaphorin (SEMA) 7A, connective tissue growth factor, integrin αvβ6, caveolin-1, let 7-d, calcium activated potassium channel KCa3.1, matrix metalloproteinase-19, lysocardiolipin acetyltransferase, dimethylarginine dimethylaminohydrolase, and transglutaminase 2. These targets have all shown the potential to modulate IPF pathophysiology, thereby inhibiting disease progression.

Conclusion: Information gained from this review will be valuable to this field, enabling the design and development of novel therapeutics for IPF.

Keywords: Idiopathic pulmonary fibrosis, novel target, genetic defects, connective tissue growth factor, matrix metalloproteinase, genome-wide assay, Integrin αvβ6, microRNA.

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Article Details

VOLUME: 24
ISSUE: 22
Year: 2017
Page: [2439 - 2458]
Pages: 20
DOI: 10.2174/0929867324666170526123607
Price: $58

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