COH34 (PARG inhibitor COH34, NSC191252) is a potent, selective and cell-active PARG inhibitor (IC50=0.37 nM).
COH34 specifically inhibits poly(ADP-ribose) glycohydrolase (PARG) and strongly binds to the catalytic domain of PARG with Asn869 as a key binding residue (Kd=0.547 uM), does not suppress the activity of PARP1 and had little impact on TARG1 at 1 uM.
COH34 suppresses the PARG-dependent dePARylation process, suppresses DNA repair in cells.
COH34 exhibits lethality in BRCA-mutant and PARP inhibitor–resistant cancer cells UWB1.289 and PEO-1 (EC50=2.1 and 0.8 uM, respectively), selectively kills BRCA-mutant and PARP inhibitor–resistant cancer cells.
COH34 exhibits antitumor activity (at 20 mg/kg) in PARP inhibitor-resistant and DNA damage repair–defective cell line xenografts.
Physicochemical Properties
M.Wt
293.384
Formula
C18H15NOS
Appearance
Solid
CAS No.
Storage
Solide Powder
-20°C 12 Months; 4°C 6 Months
In Solvent
-80°C 6 Months; -20°C 6 Months
Shipping
Solubility
10 mM in DMSO
Chemical Name/SMILES
(E)-1-(((p-tolylthio)imino)methyl)naphthalen-2-ol
References
1. Shih-Hsun Chen, et al. Sci Adv. 2019 Apr 10;5(4):eaav4340.
