Table 1 PARG inhibitors and their drawbacks

Intercalating molecules, e.g. proflavine, ethidium bromide, ethacridine

Bind PAR and resist PARG mediated hydrolysis

Not effective in-vitro and cell impermeable, IC₅₀ > 7 μM

Ex-vivo

[11, 88]

GPI16552 and GPI 18214

Same as above

Not effective in-vitro, IC₅₀ > 1.7 μM

Colon tissue mice

[11, 89]

Tannins e.g. Nobotanin K

ADPr analogs i.e. bind PAR and resist PARG

Low cell permeability, IC₅₀ > 0.3 μM

Cell line

[11, 90]

Salicylanilides

Bind PARG and inhibit dePARylation

Not effective in-vivo and non-specifically (inhibit PARP1), IC₅₀ > 12 μM

Cell line

[92]

RBPIs

Block PARG mediated PAR hydrolysis

Low specificity and less potency, IC₅₀ > 2.9 μM

Cell line

[93]

PDD00017273

Replication fork stalling and low DNA double stranded break repair

Low metabolic activity, IC₅₀ > 25 nM,

Cell line

[25, 96]

COH34

Binds PARG catalytic site and traps DDR proteins

IC₅₀ = 0.37

Mice

[24]