| Size | Price | Stock | Qty |
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| 1mg | |||
| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
PARG ( IC50 = 0.37 nM )
PARG (poly(ADP-ribose) glycohydrolase) is the primary enzyme responsible for degrading poly(ADP-ribose) (PAR) polymers synthesized by PARP enzymes. COH-34 binds to the catalytic domain of PARG with a Kd value of 0.547 microM. By inhibiting PARG, the compound prevents the removal of PAR chains, leading to persistent PARylation at DNA damage sites, which traps DNA repair factors and induces DNA damage accumulation, synthetic lethality, and cell death. |
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| ln Vitro |
COH34 effectively eliminates cancer cells resistant to PARP inhibitors[1].
COH-34 is a potent and specific PARG inhibitor with an IC50 of 0.37 nM, demonstrating high inhibitory efficiency. It binds to the catalytic domain of PARG with a Kd of 0.547 microM. The compound shows anti-tumor activity and causes lethality in cancer cells with DNA repair defects, including those deficient in homologous recombination (HR) or other DNA damage response (DDR) pathways. This synthetic lethal effect is selective for cancer cells with pre-existing DNA repair vulnerabilities. |
| ln Vivo |
COH34 shows antitumor activity and causes lethality in cancer cells with DNA repair defects in xenograft mouse cancer models[1].
COH-34 shows anti-tumor activity in xenograft mouse cancer models. The compound causes lethality in cancer cells with DNA repair defects, and this translates into tumor growth inhibition in vivo. In pre-clinical studies, COH-34 demonstrated efficacy against tumors harboring deficiencies in DNA repair pathways, such as BRCA-mutant cancers, as well as in combination with DNA-damaging agents or PARP inhibitors to overcome resistance. |
| Enzyme Assay |
The PARG enzyme activity is typically measured using a fluorometric or chemiluminescent assay that detects the removal of PAR chains. Purified recombinant human PARG enzyme is incubated with a PAR polymer substrate (e.g., PARylated histones or a synthetic PAR chain) in reaction buffer (20 mM Tris-HCl, pH 7.5, 2 mM DTT, 10 mM MgCl2) at 37degC. Varying concentrations of COH-34 are added, and after incubation, the remaining PAR chains are detected using a PAR-specific antibody in an ELISA or immunoassay format. Alternatively, a malachite green phosphate detection method can be used to measure the free ADP-ribose released.
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| Cell Assay |
Cellular assays are performed in cancer cell lines with DNA repair defects, such as BRCA1/2-deficient or HR-deficient cells. Cells are seeded in 96-well plates and treated with varying concentrations of COH-34 (0-10 microM) for 48-96 hours. Cell viability is measured using CellTiter-Glo or MTT assays to calculate synthetic lethality IC50 values. The mechanism is confirmed by Western blotting for PAR levels (using anti-PAR antibody), as well as for gammaH2AX (a marker of DNA damage). Prolonged PARylation and increased gammaH2AX signal in COH-34-treated cells confirms target engagement and DNA damage accumulation.
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| Animal Protocol |
In a xenograft mouse cancer model, female athymic nude mice are injected subcutaneously with HR-deficient cancer cells (e.g., BRCA1-mutant or DLD-1 BRCA2-/- cells). When tumors reach approximately 150-200 mm3, mice are randomized into treatment groups. COH-34 is administered via intraperitoneal injection at doses ranging from 10-50 mg/kg, typically once or twice daily for 2-3 weeks. Tumor volume is measured by calipers twice weekly. Upon study termination, tumors are harvested for PAR and gammaH2AX immunohistochemistry and Western blot analysis. Combination studies with PARP inhibitors or DNA-damaging agents are also performed.
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| ADME/Pharmacokinetics |
Specific quantitative PK parameters for COH-34 are not detailed in the literature. As a small-molecule inhibitor (MW 293.38) with potent PARG inhibition, the compound is designed for in vivo administration. Key PK properties such as bioavailability, half-life, and tissue distribution would be determined empirically. The compound is soluble in DMSO, which is typically used to prepare in vivo formulations.
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| Toxicity/Toxicokinetics |
Specific toxicological data for COH-34 are not detailed. As a PARG inhibitor that induces synthetic lethality in DNA repair-deficient cancer cells, its safety profile may be favorable because normal cells with intact DNA repair pathways are less sensitive to PARG inhibition. However, potential on-target toxicities could include effects on highly proliferative normal tissues (e.g., bone marrow, intestinal epithelium) when used at high doses or in combination with DNA-damaging agents. Standard toxicological endpoints would be assessed in animal studies.
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| References | |
| Additional Infomation |
PARG is the primary enzyme responsible for degrading PAR chains synthesized by PARP enzymes. While PARP inhibitors are clinically approved for treating HR-deficient cancers (e.g., BRCA-mutant breast and ovarian cancers), resistance to PARP inhibitors is emerging. COH-34 targets the same synthetic lethal pathway but at a different node, offering a potential strategy to overcome PARP inhibitor resistance. As of the latest updates, COH-34 is a research-grade chemical tool for studying DNA damage repair and synthetic lethality, and has not yet been approved for clinical use.
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| Molecular Formula |
C18H15NOS
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|---|---|
| Molecular Weight |
293.382803201675
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| Exact Mass |
293.09
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| Elemental Analysis |
C, 73.69; H, 5.15; N, 4.77; O, 5.45; S, 10.93
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| CAS # |
906439-72-3
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| PubChem CID |
135443632
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
351
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)S/N=C/C2=C(C=CC3=CC=CC=C32)O
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| InChi Key |
SFUAIBHPGDRCFL-XDHOZWIPSA-N
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| InChi Code |
InChI=1S/C18H15NOS/c1-13-6-9-15(10-7-13)21-19-12-17-16-5-3-2-4-14(16)8-11-18(17)20/h2-12,20H,1H3/b19-12+
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| Chemical Name |
1-[(E)-(4-methylphenyl)sulfanyliminomethyl]naphthalen-2-ol
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| Synonyms |
COH-34; COH34; COH 34
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~16.7 mg/mL (~56.8 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (5.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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