. 2024 Oct 11;77:103394. doi: 10.1016/j.redox.2024.103394

Table 1.

List of MTH1 inhibitors.

S. No.	Inhibitors	Class	IC₅₀ values	Treatment time and cell types	Methods	Functions	References
1.	Echinacoside	phenol	7 μmol/L	12 h s and Human MG63 osteosarcoma, SK-HEP-1 hepatocarcinoma, MCF7 breast cancer, SW480 colorectal cancer	Colony formation assay, MTT assay, Western blot, DAPI-stained nuclei	Increased oxidative damage and P21 overexpression	[153]
2.	FP 1-8	farnesyl phenolic	8.6–28.5 μmol/L	48 h s, U2OS, SW620, ES-2,	CCK8 assay method, Cellular thermal shift assay (CETSA)	Induced DNA damage and obstruct DNA replication in cancer cells	[154]
3.	α-mangostin	xanthone	0.47 μmol/L	30 min s	Malachite green inhibition assay	Binds to the active site of MTH1 and inhibits its activity	[155]
4.	3-isomangostin	xanthone	52 nmol/L	30 min s	Malachite green inhibition assay	Possess strong MTH1 inhibitory potency	[155]
5.	Thymoquinone	flavonoids	13.5 μM	72 h s, MCF7 breast cancer	MTT assay, annexin-V and Calcein-AM/PI double staining and MitoSOXTM Red staining	Impose oxidative stress leading to cell death.	[71]
6.	Baicalin	flavonoids	38.9 μM	72 h s, MCF7 breast cancer		Binds to the active site and inhibits MTH1 activity	[71]
7.	Fisetin	flavonoids	33.67 μM	24 h s, squamous cell carcinoma cell line A431	MTT assay, colony formation assay, Cell migration assay, DCFH-DA dye, TMRM dye	Induces apoptosis by downregulating MTH1	[156]
8.	Emodin	hydroxy-anthraquinone	32.71 μM	72 h, NSCLC and A549	Mitochondrial Membrane Potential (ΔΨM) Assay, Annexin V/PI Apoptosis Analysis, Comet Assay, TUNEL assay	Elevate ROS burden and inhibit dNTP pool sanitization	[157]
9.	TH287	Pyrimidine Analogues	0.8 nmol/L	24 h, BGC-823 and SGC-7901	Transwell and scratch assays, JC-1 staining,	Affect mitochondrial function and block PI3K/AKT signaling	[14,85,[158], [159], [160]]
10.	TH588		7.0 nmol/L	Human pancreatic carcinoma (MIAPaCa-2 and Panc-1), lymphoma (BALM3), and leukemia (NB4)	MTT assay, FITC-labeled avidin immunofluorescence experiments	Inhibit microtubule polymerization	[14,85,158,160]
11.	TH1579					obstructs mitosis and trigger spindle assembly checkpoint	[56,105,149,161,162]
12.	Crizotinib	Small molecule inhibitors	1.4–4.3 μmol/L	24–72 h, A549, HCC and H1975	MTT, XTT, or WST-1 assay, Annexin V/PI Staining, TUNEL Assay	targets ALK, HGFR, c-MET), ROS1 (c-ros)	[[163], [164], [165]]
13.	(S)-Crizotinib		330 nmol/L	24–72 h, A549, HCC and H1975		induces the accumulation of DNA single-strand breaks	[107,166,167]
14.	SCH 5 1344		410 nmol/L	2–3 days, KRAS tumor cells	Silencing of MTH1 by siRNA	inhibit RAS-overexpressing fibroblast growth	[15]
15.	Imiquimod (TLR7 agonist)		0.65 μmol/L	72 h s, precancerous dysplastic oral keratinocyte (DOK) cell line, squamous cell carcinoma cell line A431	MTT viability assay, Annexin V and 7-aminoactinomycin D (7AAD) double staining,	Induces cytokine production	[15,145]
16.	Resiquimod (TLR7 agonist)					produce antiviral cytokines, including IFN-α and TNF-α	[15,168]
16.	Amino pyrimidines, AP1-12	Pyrimidine Analogues	0.2 nmol/L to 4 μmol/L		dGTP was used to determine the IC₅₀ values.	Inhibit MTH1 by binding to the active site of MTH1	[15,169]
17.	MI-743		91.44 nmol/L	72 h s, gastric cancer cell lines MGC-803 and HGC-27 cells,	cellular thermal shift assay (CETSA)	Trigger DDR and apoptosis	[13,102,170]
18.	MI-401		461.32 nmol/L			build-up of 8-oxo-dG lesions	[13,102,170]
19.	purinone (P) analogues, P1-2	Purine analogues	2.8 μmol/L	P-2, PM-1 and PM-3 tested in K562 cells by CETSA.	dGTP was used for determining the IC₅₀ values	Inhibit MTH1 activity	[15,168]
20.	purinone macrocycle analog, PM1-5		0.3 nmol/L to 1.4 nmol/L	P-2, PM-1 and PM-3 tested in K562 cells by CETSA.		increase inhibitory effectiveness against MTH1	[15,168]
21.	fragments docked against MTH1 binding site, F1-5		6–79 μmol/L			Binds to the active site and inhibit MTH1 activity	[15,171]
22.	Purine derivatives Pu1-8		3.3 to 0.21 μmol/L	Pu-3 and Pu-5: HeLa cells	target engagement assay	Binds MTH1 and induce DNA damage	[15,172,173]
23.	3-amidoquinolines (AQ), AQ1-12	Quinoline and quinazoline analoguesa	0.9 nmol/L to 9 nmol/L		dGTP was used for determining the IC₅₀ values	Enhanced inhibitory potency against MTH1	[15,168]
24.	2-aminoquinazoline (AZ), AZ1-4	Quinoline and quinazoline analoguesa	3.32 μmol/L to 9 nmol/L		dGTP was used for determining the IC₅₀ values	Binds to the active site and inhibit MTH1 activity	[15,168]
25.	7-azaindole (AI), AI1-15	Indole and indazole analogues	5 nmol/L to 23 μmol/L	AI-13 (BAY-707)	Caco-2 Permeability Assay	Binds to the active site and inhibit MTH1 activity	[15,174]
26.	7-azaindazole (AID) analogues, AID1-5	Indole and indazole analogues	1–30 nmol/L	AI-13 (BAY-707)	Caco-2 Permeability Assay	Accumulation of 8-oxoG concentrations, DNA damage, ensuing cell death	[15,174]
27.	7-deazadGTP	Nucleotide analogues, 8-halogenated 7-deazadGTP analogues	1.57 μmol/L			Competitive inhibition with 8-oxo-dGTP,	[175,176]
28.	7-I-7-deazadGTP		2.62 μmol/L	24 h s, HeLa cells	cell titer assay
29.	8-Cl-7-deazadGTP		0.857 μmol/L		dGTP was used for determining the IC₅₀ values
30.	8-Br-7-deazadGTP		0.496 μmol/L
31.	8-I-7-deazadGTP		0.415 μmol/L
32.	Cd (II) and Cu (II)	Metalated analogues	30 and 17 μmol/L	2 h s, CHO cells	HPLC	Enhanced levels of 8-oxo-dG lesion in DNA	[15,177]
33.	CR1-4	Metalated analogues	151 μmol/L to 6 nmol/L	8-oxo-dGTP was used for determining the IC₅₀ values	HPLC	Binds to the active site and suppress MTH1 activity	[178]