Table 4.

Inhibitors for the treatment of pancreatic cancer

Drug type	Drug name	Active site	Mechanism	Effect	Targeting tumors
Relating to histone methyltransferase	SMYD3 inhibitor piperidine-4-formamide-acetylaniline compound (BCI-121)	It competes with histones to bind SMYD3, binding sites are formed within the SET and post-SET fingers and contained in a deep and narrow substrate binding cavity	BCI-121 is a competitive inhibitor significantly inhibits; SMYD3-substrate interaction and chromatin recruitment	It inhibits cancer cell growth and accumulates during the cell cycle S	High expression of SMYD3 protein in cancer cell lines (pancreatic cancer, lung, prostate and ovarian cancer)[173]
	PRMT5 inhibitor EZP015556	MTAP	-	It works for MTAP He and MTAP PDO	A negative tumor MTAP (a commonly lost gene in pancreatic cancer)[174]
	EZH2 inhibitor 3-Dazocycline A (DZNeP)	It regulates EZH2 and H3K27me3 protein expression	DZNeP inhibit the activity of S-adenosine-L-homocysteine (AdoHcy) hydrolase, which reversely hydrolyzes AdoHcy to adenosine and homocysteine, thereby inhibiting histone methylation	It synergistically enhanced antiproliferative activity of gemcitabine and significantly increased apoptosis rate	Pancreatic ductal carcinoma[175]
Relating to histone demethylase	BET inhibitor JQ1 related to KDM6A	Reducing activity and p63 levels of MYC pathways	GLI1 is the main target gene of the Hh pathway JQ1 reduces the mRNA and protein levels of primary human CAFs. TGF-β is an interstitial activator that JQ1 its induced response	Altered KMT2C (MLL3)-KDM6A (UTX)- PRC2 regulating axis	Pancreatic ductal carcinoma[169,176,177]

All current research on inhibitors for the treatment of pancreatic cancer developed based on histone methylation modification. “-” means that the content does not exist here. This table is sorted according to the correlation with histone methyltransferases and demethylases. CAF: Cancer-associated fibroblast; KMT: Histone lysine methyltransferases; PDO: Patient-derived organoid; PRC2: Polycomb repressive complex 2; TGF-β: Transforming growth factor β.