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COH34 Sale

目录号 : GC39282

COH34 是一种有效且特异性的聚 (ADP-核糖) 糖水解酶 (PARG) 抑制剂,IC50为 0.37 nM。COH34 与 PARG 的催化结构域 (Kd= 0.547 μM) 结合,从而延长了 DNA 损伤处的 PARylation 并捕获了 DNA 修复因子。

COH34 Chemical Structure

Cas No.:906439-72-3

规格 价格 库存 购买数量
5mg
¥3,150.00
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10mg
¥4,950.00
现货
50mg
¥14,850.00
现货
100mg
¥20,250.00
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Sample solution is provided at 25 µL, 10mM.

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产品描述

COH34 is a potent and specific poly(ADP-ribose) glycohydrolase (PARG) inhibitor with an IC50 of 0.37 nM. COH34 binds to the catalytic domain of PARG (Kd=0.547 μM), thereby prolonging PARylation at DNA lesions and trapping DNA repair factors[1].

[1]. Chen SH, et al. Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Sci Adv. 2019 Apr 10;5(4):eaav4340.

Chemical Properties

Cas No. 906439-72-3 SDF
Canonical SMILES CC1=CC=C(S/N=C/C2=C3C=CC=CC3=CC=C2O)C=C1
分子式 C18H15NOS 分子量 293.38
溶解度 DMSO: 16.67 mg/mL (56.82 mM) 储存条件 Store at -20°C,unstable in solution, ready to use.
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1 mg 5 mg 10 mg
1 mM 3.4085 mL 17.0427 mL 34.0855 mL
5 mM 0.6817 mL 3.4085 mL 6.8171 mL
10 mM 0.3409 mL 1.7043 mL 3.4085 mL
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Research Update

Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies

Sci Adv 2019 Apr 10;5(4):eaav4340.PMID:30989114DOI:10.1126/sciadv.aav4340.

While poly(ADP-ribosyl)ation (PARylation) plays an important role in DNA repair, the role of dePARylation in DNA repair remains elusive. Here, we report that a novel small molecule identified from the NCI database, COH34, specifically inhibits poly(ADP-ribose) glycohydrolase (PARG), the major dePARylation enzyme, with nanomolar potency in vitro and in vivo. COH34 binds to the catalytic domain of PARG, thereby prolonging PARylation at DNA lesions and trapping DNA repair factors. This compound induces lethality in cancer cells with DNA repair defects and exhibits antitumor activity in xenograft mouse cancer models. Moreover, COH34 can sensitize tumor cells with DNA repair defects to other DNA-damaging agents, such as topoisomerase I inhibitors and DNA-alkylating agents, which are widely used in cancer chemotherapy. Notably, COH34 also efficiently kills PARP inhibitor-resistant cancer cells. Together, our study reveals the molecular mechanism of PARG in DNA repair and provides an effective strategy for future cancer therapies.

Genomic and biological aspects of resistance to selective poly(ADP-ribose) glycohydrolase inhibitor PDD00017273 in human colorectal cancer cells

Cancer Rep (Hoboken) 2023 Feb;6(2):e1709.PMID:36053937DOI:10.1002/cnr2.1709.

Background: Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme in poly(ADP-ribose) (PAR) metabolism and a potential anticancer target. Many drug candidates have been developed to inhibit its enzymatic activity. Additionally, PDD00017273 is an effective and selective inhibitor of PARG at the first cellular level. Aims: Using human colorectal cancer (CRC) HCT116 cells, we investigated the molecular mechanisms and tumor biological aspects of the resistance to PDD00017273. Methods and results: HCT116RPDD , a variant of the human CRC cell line HCT116, exhibits resistance to the PARG inhibitor PDD00017273. HCT116RPDD cells contained specific mutations of PARG and PARP1, namely, PARG mutation Glu352Gln and PARP1 mutation Lys134Asn, as revealed by exome sequencing. Notably, the levels of PARG protein were comparable between HCT116RPDD and HCT116. In contrast, the PARP1 protein levels in HCT116RPDD were significantly lower than those in HCT116. Consequently, the levels of intracellular poly(ADP-ribosyl)ation were elevated in HCT116RPDD compared to HCT116. Interestingly, HCT116RPDD cells did not exhibit cross-resistance to COH34, an additional PARG inhibitor. Conclusion: Our findings suggest that the mutated PARG acquires PDD00017273 resistance due to structural modifications. In addition, our findings indicate that PDD00017273 resistance induces mutation and PARP downregulation. These discoveries collectively provide a better understanding of the anticancer candidate PARG inhibitors in terms of resistance mechanisms and anticancer strategies.