Pirfenidone (Synonyms: AMR 69)

Pirfenidone (AMR69) is an orally active antifibrotic drug that attenuates the production of chemokines CCL2 and CCL12 in fibrocytes^[1]. Pirfenidone is a synthetic pyridone drug used to treat idiopathic pulmonary fibrosis (IPF) and also has anti-inflammatory and antioxidant properties ^[2].

In vitro, pirfenidone (1-10 mM) treatment of human glioma cell lines (LN-18, T98G, LNT-229, and LN-308) for 48 h reduced cell proliferation in a concentration-dependent manner, reduced the levels of the intracellular cytokine transforming growth factor (TGF-β), and reduced the levels of matrix metalloproteinase (MMP-11) ^[3]. Pirfenidone (2mg/mL) treated intestinal fibroblasts (p-hIFs) for 72 hours reversibly inhibited cell proliferation, inhibited the expression of extracellular matrix proteins (ECM), and inhibited the phosphorylation of the TGF-β1/mTOR/p70S6K signaling pathway mediated by TGF-β1^[4].

In vivo, oral treatment of chronic graft-versus-host disease (cGVHD) mice with pirfenidone (400 mg/kg) effectively reduced macrophage infiltration and TGF-β production, and reduced fibrosis and tissue damage in the skin and visceral organs^[5]. Oral treatment of idiopathic pulmonary fibrosis (IPF) mice with pirfenidone (300 mg/kg) significantly slowed the progression of pulmonary fibrosis, reduced the mRNA levels of TGF-β, fibronectin and other fibrosis-related genes, and reduced collagen deposition^[6].

References:
[1] Inomata M, Kamio K, Azuma A, et al. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis[J]. Respiratory research, 2014, 15: 1-14.
[2] Antar S A, Saleh M A, Al-Karmalawy A A. Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2[J]. Life Sciences, 2022, 309: 121048.
[3] Burghardt I, Tritschler F, Opitz C A, et al. Pirfenidone inhibits TGF-β expression in malignant glioma cells[J]. Biochemical and biophysical research communications, 2007, 354(2): 542-547.
[4] Cui Y, Zhang M, Leng C, et al. Pirfenidone inhibits cell proliferation and collagen I production of primary human intestinal fibroblasts[J]. Cells, 2020, 9(3): 775.
[5] Du J, Paz K, Flynn R, et al. Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production[J]. Blood, The Journal of the American Society of Hematology, 2017, 129(18): 2570-2580.
[6] Duerr J, Leitz D H W, Szczygiel M, et al. Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice[J]. Nature communications, 2020, 11(1): 2012.