| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
PARG-IN-4 targets PARG (poly(ADP-ribose) glycohydrolase), the primary enzyme responsible for the degradation of poly(ADP-ribose) (PAR) chains. PAR chains are synthesized by poly(ADP-ribose) polymerases (PARPs) in response to DNA damage. By inhibiting PARG, the compound prevents the hydrolysis of PAR chains, leading to the accumulation of PAR and prolonged PARP activity. This disrupts DNA damage repair and induces cell death in cancer cells.
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| ln Vitro |
In vitro, PARG-IN-4 demonstrates potent PARG inhibitory activity with an EC₅₀ of 1.9 nM. The compound is cell-permeable and can effectively inhibit PARG activity in cells. By inhibiting PARG, the compound disrupts DNA damage repair pathways, leading to anti-proliferative effects in cancer cells. The compound is soluble in DMSO at 12 mg/mL.
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| ln Vivo |
In vivo, PARG-IN-4 is orally active and effectively inhibits tumor growth in mouse models. The compound's oral bioavailability enables convenient administration in preclinical studies. Its ability to inhibit tumor growth in vivo supports its potential as a therapeutic agent for cancer. The compound can be used in cancer research to study the role of PARG in DNA damage repair and tumor progression.
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| Enzyme Assay |
For non-cellular in vitro enzyme assays, PARG-IN-4 is evaluated for its inhibitory activity against purified PARG. The compound is incubated with PARG and a poly(ADP-ribose) substrate, and the hydrolysis of PAR chains is measured. The EC₅₀ for PARG inhibition is determined from dose-response curves, with a value of 1.9 nM.
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| Cell Assay |
For in vitro cellular assays, PARG-IN-4 is tested in cancer cell lines to assess its effects on PAR metabolism and cell viability. Cells are treated with serial dilutions of the compound, and PAR levels are measured by immunofluorescence or Western blot using anti-PAR antibodies. Cell viability and proliferation are measured using standard assays. The compound's effects on DNA damage repair are evaluated.
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| Animal Protocol |
For in vivo animal studies, PARG-IN-4 is evaluated in xenograft mouse models of cancer. Mice bearing established tumors are treated with the compound via oral administration at various doses. Tumor volumes are measured regularly, and tumor growth inhibition is calculated. PAR levels and DNA damage markers are assessed in tumor tissues at study endpoint. Body weight and general health are monitored to evaluate tolerability.
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| ADME/Pharmacokinetics |
PARG-IN-4 is orally active with favorable pharmacokinetic properties. The compound's oral bioavailability enables convenient administration in preclinical studies. It is soluble in DMSO at 12 mg/mL and can be formulated for in vivo administration. Powder can be stored at -20°C for 3 years or at 4°C for 2 years. Information concerning product stability, particularly in solution, has rarely been reported.
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| Toxicity/Toxicokinetics |
Toxicological data for PARG-IN-4 are limited. As a PARG inhibitor that disrupts DNA damage repair, the compound may have on-target effects on normal cellular functions. Comprehensive toxicology studies including acute and repeat-dose toxicity, genotoxicity, and organ-specific toxicity assessments would be required for therapeutic development. The compound is for research use only and not for human use.
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| References | |
| Additional Infomation |
PARG-IN-4 (Formula A) is a selective, orally active, and cell-permeable PARG inhibitor with an EC₅₀ of 1.9 nM. PARG is a key enzyme responsible for hydrolyzing poly(ADP-ribose) chains in the DNA damage response pathway. The compound effectively inhibits tumor growth in mouse models and can be used in cancer research. It has a molecular weight of 457.46 and molecular formula C₂₃H₂₀FN₇O₃.
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| Exact Mass |
497.148
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|---|---|
| CAS # |
2988890-20-4
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| PubChem CID |
169078314
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
818
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1CN(C[C@@H](N1)C)C2=CC(=CC3=C2C=NN3C4=NN=C(S4)C(F)F)S(=O)(=O)NC5(CC5)C
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| InChi Key |
AQOUTSJIZZVANZ-RYUDHWBXSA-N
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| InChi Code |
InChI=1S/C20H25F2N7O2S2/c1-11-9-28(10-12(2)24-11)15-6-13(33(30,31)27-20(3)4-5-20)7-16-14(15)8-23-29(16)19-26-25-18(32-19)17(21)22/h6-8,11-12,17,24,27H,4-5,9-10H2,1-3H3/t11-,12-/m0/s1
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| Chemical Name |
1-[5-(difluoromethyl)-1,3,4-thiadiazol-2-yl]-4-[(3S,5S)-3,5-dimethylpiperazin-1-yl]-N-(1-methylcyclopropyl)indazole-6-sulfonamide
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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