Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) without an identifiable cause. If not treated after diagnosis, the average life expectancy is 3–5 years. Currently approved drugs for the treatment of IPF are Pirfenidone and Nintedanib, as antifibrotic drugs, which can reduce the decline rate of forced vital capacity (FVC) and reduce the risk of acute exacerbation of IPF. However these drugs can not relieve the symptoms associated with IPF, nor improve the overall survival rate of IPF patients. We need to develop new, safe and effective drugs to treat pulmonary fibrosis. Previous studies have shown that cyclic nucleotides participate in the pathway and play an essential role in the process of pulmonary fibrosis. Phosphodiesterase (PDEs) is involved in cyclic nucleotide metabolism, so PDE inhibitors are candidates for pulmonary fibrosis. This paper reviews the research progress of PDE inhibitors related to pulmonary fibrosis, so as to provide ideas for the development of anti-pulmonary fibrosis drugs.

Targeting glutamate metabolism in chronic lung diseases

“…Despite important advances in therapy for these lung diseases, there remain unmet clinical needs for targeted and highly effective treatment. Metabolomics, which focuses on small molecule metabolites such as amino acids (AAs), lipids, fatty acids and carbohydrates, holds great promise for identifying biomarkers for chronic lung diseases due to its high sensitivity, specificity and accuracy 3–6 . Maintaining metabolic homeostasis is crucial for normal cellular structure and function, as any imbalance can lead to various cell injuries and even cell death, ultimately affecting the integrity of lung function and contributing to the development of lung diseases.…”

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

“…2,3 Reversing tissue remodeling and functional decline caused by ECM deposition is an important therapeutic strategy in fibrotic diseases. 15 Notably, while ECM degradation is beneficial to patients, it also generates bioactive ECM fragments called matricryptins, which interact with cell surface receptors and regulate inflammatory, fibrogenic, and reparative cascades. 16,17 Elastin, a key component of the ECM, can be degraded by elastases to generate elastin-derived peptides (EDPs).…”

“…IPF is characterized by the destruction of alveolar architecture and excessive deposition of ECM proteins. , Reversing tissue remodeling and functional decline caused by ECM deposition is an important therapeutic strategy in fibrotic diseases . Notably, while ECM degradation is beneficial to patients, it also generates bioactive ECM fragments called matricryptins, which interact with cell surface receptors and regulate inflammatory, fibrogenic, and reparative cascades. , Elastin, a key component of the ECM, can be degraded by elastases to generate elastin-derived peptides (EDPs). − These bioactive peptides exhibit a wide range of biological activities in various pathophysiological processes, including cell proliferation, protease gene expression, fibrotic diseases, as well as vascular and metabolic diseases. − When bound to the elastin-binding protein (EBP) subunit of the elastin receptor complex (ERC), EDPs initiate a new fibrotic cycle. − The ERC consists of EBP, protective protein/cathepsin A (PPCA), and neuraminidase-1 (NEU-1), playing a fundamental role in signaling transduction.…”

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

“…However, the pathogenesis of IPF is complex and unclear at present. This leads to a lack of effective treatment options for IPF other than lung transplantation, and even nintedanib and pirfenidone only delay the progression of the disease (Yang et al 2023 ). In addition to fibroblasts, IPF is also related to the pathological changes of lung epithelial cells (LECs), mainly including alveolar and bronchial epithelial cells (Fujishima et al 2010 ; Cabrera et al 2015 ).…”