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Table 8 Pharmacotherapy for IPF: agents in current clinical trials

From: Diagnosis and management of interstitial lung disease

Agent Target Rationale
Pirfenidone TGF-β, PDGF Down-regulation of TGF-β-stimulated collagen synthesis and extracellular matrix accumulation and PDGF proliferative effects on fibroblasts
Tyrosine kinase inhibitors Tyrosine kinase receptors Inhibit fibrinogenic pathways by inhibiting receptor tyrosine kinase (RTK) binding by ligands (e.g. TGF-β, PDGF-B, CTGF, FGF, VEGF)
N-acetylcysteine ROI (oxidant-antioxidant imbalance) Replenish pulmonary glutathione stores and thereby antagonize signaling and tissue damaging effects of oxygen radicals (e.g. stimulatory effects of ROI on myofibroblasts)
Anti-TGF-β TGF-β Block TGF-β-induced fibroblast migration & proliferation, differentiation of myofibroblasts into fibroblasts, epithelial-mesenchymal transition, and resistance of myofibroblasts to apoptosis
Anti-CTGF CTGF Suppress fibroblast stimulation by CTGF
Anti-IL-13 IL-13 Inhibit induction of profibrotic cytokines (e.g. TGF-β, PDGF, IGF-1, PDGF, MMP-9)
Anti-LPA Lysophosphatidic acid (LPA) Prevent fibroblast recruitment into lung interstitium that can occur via the G protein-coupled LPA1 receptor
Anti-CCL2 CCL-2 Inhibit cell (e.g. lymphocytes, monocytes, fibrocytes) chemotaxis/influx to lung tissue and TGF-β expression
Anti-LOXL2 Lysyl oxidase-like protein-2 (LOXL-2) Inhibit LOXL2-mediated fibroblast activation and deposition/accumulation of collagen
Plasma exchange, rituximab, steroids Immune/inflammatory mediators Suppress inflammation associated with an episode of acute exacerbation of IPF
  1. Abbreviations: TGF-β transforming growth factor-β, TNF-α tumor necrosis factor-α, ROI reactive oxygen intermediates, CTGF connective tissue growth factor, PH pulmonary hypertension.