RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Table 4 Strategies for targeting ALKBH5 in cancer

Strategy	Function	Compounds/Methods	Preclinical models	Ref
Small-molecule modulators	Specific inhibitor	2-[(1-hydroxy-2-oxo-2-phenylethyl)sulfanyl]acetic acid	Leukemia and GBM cell lines	[162]
		4-[(furan-2-yl)methyl]amino-1,2-diazinane-3,6-dione	Leukemia and GBM cell lines	[162]
		ALK-04	Murine B16 melanoma model	[133]
	Non-specific inhibitor	MV1035	GBM cell lines	[163]
	Specific activator	Identifying potential compounds by high-throughput screening	–	NR
Proteolysis targeting chimera	ALKBH5 degradation	Linking a ligand of ALKBH5 protein with a ligand of an E3 ubiquitin ligase	–	NR
CRISPR-based site-specific m⁶A editing	m⁶A demethylation	dm⁶ACRISPR	HeLa cells	[171]
CRISPR-based site-specific m⁶A editing	m⁶A methylation	dCas13-M3nls, dCas13-M3M14nes	HEK293T cells	[174]
Targeting ALKBH5 regulators	ALKBH5 suppression	5-azacytidine	Lung cancer cell lines	[89]
		C646	UM cell lines	[108]
		miR-193a-3p mimic	Glioma and ESCC cell lines	[78, 149]
	ALKBH5 restoration	Targeting negative regulators of ALKBH5	–	NR
Gene therapy	ALKBH5 restoration	Delivering ALKBH5 gene by viral vectors	–	NR

GBM Glioblastoma, UM Uveal melanoma, ESCC Esophageal squamous cell carcinoma, NR not reported

ISSN: 1756-8722