Pirfenidone, Fluorofenidone and New Antifibrotic Drugs: Biochemistry of Direct and Indirect Effects

As a broad spectrum antifibrotic agent, pirfenidone has been shown to be efficacious in many patients and models of fibrotic diseases including idiopathic pulmonary fibrosis (IPF).Discovery of pirfenidone, along with nintedanib, was a significant progress in fight against IPF, a chronic, progressive disease of uncertain etiology.Pirfenidone has shown antifibrotic and antiinflammatory effects in various models, but its molecular target has not been elucidated.It is plausible that pirfenidone interacts with multiple target molecules.Fluorofenidone and other structurally-related compounds are also gaining researchers' interest for their high potencies in in vitro antifibrotic effects.This review article is aimed to overview recent researches on pirfenidone and some other antifibrotic compounds with a focus on biochemical mechanisms.In particular, potential importance of the antioxidative activities of these drugs in possible linkage to anti-inflammatory and anti-fibrogenic effects are considered.In addition, novel modalities of pirfenidone effects in collagen fibril formation and effects mediated by regulator of G-protein signalling 2 (RGS2) and hedgehog signalling are discussed.