. 2021 Jul 27;13(8):1463. doi: 10.3390/v13081463

Table 1.

Reported inhibitors of various DNA repair factors that reduce cccDNA levels in biochemical and cell culture assays.

Inhibitor	Target	Effects on cccDNA Biogenesis	Effective Dose Tested	System Used	References
Aphidicolin	DNA polymerases POLδ, POLα, and POLε	Specifically inhibits the synthesis of the plus strand	100 μM	Biochemical	[19,75]
Aphidicolin	DNA polymerases POLδ, POLα, and POLε	Reduced de novo cccDNA formation and amplification	100–400 μM for de novo formation; 1 μM for intracellular amplification	hNTCP-HepG2 and HepAD38 cell lines	[33,75]
p21 peptide	PCNA-POLδ interaction	Specifically inhibits the synthesis of the plus strand	100 μM	Biochemical	[19]
PTPD	FEN-1 endonuclease	Reduced de novo cccDNA formation and its amplification	5–20 μM	hNTCP-HepG2 and Hep38.7-Tet cell lines	[19,77]
Topotecan	TOP1	Reduced cccDNA intracellular amplification	0.1–4 μM	HepAD38	[104]
Camptothecin	TOP1	Same as above	0.06–2 μM	HepAD38	[104]
Idarubicin	TOP2	Same as above	16–250 nM	HepAD38	[104]
Doxorubincin	TOP2	Same as above	62–250 nM	HepAD38	[104]
Aclarubicin	TOP2	Same as above	250–1000 nM	HepAD38	[104]
Mitoxantrone	TOP2	Same as above	500 nM	HepAD38	[104]
Merbarone	TOP2	Same as above	6–100 μM	HepAD38	[104]
L1	LIG1 and LIG3	Inhibits cccDNA formation	20 μM	Biochemical	[50,147,148]
L25	LIG1 and LIG3	Inhibits cccDNA formation	25 μM	Biochemical	[50,147,148]
L189	LIG1, LIG3, and LIG4	Inhibits cccDNA formation	50 μM	Biochemical	[50,147,148]
L189	LIG1, LIG3, and LIG4	Reduced cccDNA amplification in cell culture	10–20 μM	Tet- inducible HepDG10 cells	[50,147,148]
AZD6738	ATR	Reduced de novo cccDNA formation and intracellular amplification	25–50 μM	hNTCP-HepG2, AML12HBV10, and primary human hepatocytes	[133]
VE-821	ATR	Reduced de novo cccDNA formation and intracellular amplification	5–10 μM	hNTCP-HepG2, AML12HBV10	[133]
CGK733	ATM and ATR	Reduced de novo cccDNA formation	1–12 μM	hNTCP-HepG2, and primary human hepatocytes	[133]
Torin2	ATM and ATR	Reduced de novo cccDNA formation and intracellular amplification	0.03–1 μM	hNTCP-HepG2, AML12HBV10, and primary human hepatocytes	[133]
PF477736	CHK1 and CHK2	Reduced cccDNA intracellular amplification	8 μM	AML12HBV10	[133]
CHIR-124	CHK1	Reduced de novo cccDNA formation and intracellular amplification	1–4 μM	hNTCP-HepG2, HepAD38, AML12HBV10, and primary human hepatocytes	[133]