TABLE 3.

Drugs targeting histone modification in IPF.

Drugs	Targets	Cell or animal model	Mechanism of action	Ref
3-DZNeP	EZH2/G9a inhibitor	BLM mice and LL29 cell	Reduce p-Smad2/3 nuclear translocations in vitro and downregulate α-SMA, COL1A1 and COL3A1 expression in vivo. Restore COX-2 expression and PGE2 production	Coward et al. (2014); Xiao et al. (2016)
A6	p300i	BLM mice; lung fibroblast cells	Decrease histone acetylation and pro-fibrotic gene expression in vitro, and reduce collagen deposition in vivo	Hwang et al. (2020)
Ac-SDKP	α-TAT1	MRC5/A549 cell	Promote apoptosis	Shifeng et al. (2019)
Romidepsin	HDACi	BLM mice	Inhibit LOX expression	Conforti et al. (2017)
LBH589	pan-HDACi	Primary IPF	Reduce expression of genes associated with ECM synthesis, proliferation and cell survival and suppress HDAC7 level	Korfei et al. (2015)
CG-745	HDACi	BLM/PHMG mice	Inhibit collagen production, inflammatory cell accumulation, and cytokines release	Kim et al. (2019)
Entinostat and vorinostat	HDACi	HFL-1 cell	Upregulate XPLN mRNA expression and reverse TGF-β-induced SPARC expression	Kamio et al. (2017)
TSA	pan-HDACi	NHLF cell	Reduce p-Akt level to inhibit TGF-β-mediated α-SMA expression	Guo et al. (2009)
SAHA	pan-HDACi	HLF cell	Promote the differentiation of fibroblasts into myofibroblasts and collagen deposition	Z Wang et al. (2009)
SpA	HDACi	Primary IPF	Inhibit the proliferation of IPF fibroblasts by increasing p21 expression	Davies et al. (2012)
JQ1	Bromodomain protein inhibitor	IPF fibroblasts	Bromodomain protein is the “Reader” of acetylated lysine in histone, and it is the only protein domain that can recognize and bind acetylated lysine in histone	Filippakopoulos et al. (2010)