Table 4.
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.