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Table 1 PARG inhibitors and their drawbacks

From: Targeting dePARylation for cancer therapy

Inhibitor Activity Limitations and IC50 Cancer type/model References
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]