Tags

Type your tag names separated by a space and hit enter

Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective.
Curr Med Chem 2017; 24(22):2439-2458CM

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.

Authors+Show Affiliations

School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S Coulter, Amarillo, TX 79106, United States.School of Pharmacy Keck Graduate Institute, 535 Watson Drive, Claremont, CA - 91711, United States.College of Pharmacy and Health Sciences St. John's University, 8000 Utopia Parkway, Queens, NY - 11439, United States.College of Pharmacy and Health Sciences St. John's University, 8000 Utopia Parkway, Queens, NY - 11439, United States.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28552057

Citation

Vaidya, Bhuvaneshwar, et al. "Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: a Drug Discovery Perspective." Current Medicinal Chemistry, vol. 24, no. 22, 2017, pp. 2439-2458.
Vaidya B, Patel R, Muth A, et al. Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective. Curr Med Chem. 2017;24(22):2439-2458.
Vaidya, B., Patel, R., Muth, A., & Gupta, V. (2017). Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective. Current Medicinal Chemistry, 24(22), pp. 2439-2458. doi:10.2174/0929867324666170526123607.
Vaidya B, et al. Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: a Drug Discovery Perspective. Curr Med Chem. 2017;24(22):2439-2458. PubMed PMID: 28552057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective. AU - Vaidya,Bhuvaneshwar, AU - Patel,Ruaab, AU - Muth,Aaron, AU - Gupta,Vivek, PY - 2017/01/03/received PY - 2017/03/31/revised PY - 1970/01/01/accepted PY - 2017/5/30/pubmed PY - 2017/9/13/medline PY - 2017/5/30/entrez KW - Idiopathic pulmonary fibrosis KW - Integrin αvβ6 KW - connective tissue growth factor KW - genetic defects KW - genome-wide assay KW - matrix metalloproteinase KW - microRNA KW - novel target SP - 2439 EP - 2458 JF - Current medicinal chemistry JO - Curr. Med. Chem. VL - 24 IS - 22 N2 - 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. SN - 1875-533X UR - https://www.unboundmedicine.com/medline/citation/28552057/Exploitation_of_Novel_Molecular_Targets_to_Treat_Idiopathic_Pulmonary_Fibrosis:_A_Drug_Discovery_Perspective_ L2 - http://www.eurekaselect.com/152717/article DB - PRIME DP - Unbound Medicine ER -