Table 3.

The inhibitors of SIRT6.

Categories and names		Mechanisms	Functions	Ref.
Quinazolinediones	SYN17739303	All quinazolinediones bind the NAM-binding pocket, inhibiting the deacetylase activity of SIRT6; increase GLUT1 expression and reduce TNF-α secretion	Improves oral glucose tolerance, lowers blood glucose in T2DM; inhibits inflammatory responses	[114, 223, 257, 258]
Salicylates	OSS-128167	The salicylic moiety interacts with the NAM-binding pocket of SIRT6, inhibiting its deacetylase activity; reduces TNF-α secretion	Increases glucose uptake; sensitizes cancer cells to DNA damage agents; promotes cellular apoptosis in diffuse large B-cell lymphoma cells through inhibiting SIRT6-induced activation of PI3K/Akt/mTOR signaling pathway	[223, 259]
Trichostatin A		Binds the NAM pocket and acyl channel to inhibit SIRT6 deacetylase activity; increases p53K382 acetylation level	Increasing cellular apoptosis under stress resistance	[224, 225]
Catechin gallate		Binds the acyl channel to inhibit SIRT6 deacetylase activity	Not reported	[207]
A127-(CONHPr)-B178		Binds the NAD+ pocket to inhibit demyristoylase activity (IC50=6.7 μmol)	Promotes DNA damage, senescence and cell apoptosis	[226]
Lysine-based peptides	BH-TM4	A modified lysine residue binds the Nε-acetyl lysine-binding site, inhibiting both the deacetylase (IC50=8.2 μmol) and demyristoylase (IC50=1.7 μmol) activities of SIRT6	Not reported	[229]
	Cyclic peptide	Inhibits the demyristoylase activity (IC50=0.319 μmol) of SIRT6	Not reported	[230]
5-(4-Methylpiperazin-1-yl)-2-nitroaniline		Inhibits SIRT6 deacetylase activity (IC50= 4.93 μmol); promotes GLUT1 levels	Reduces blood glucose	[115]