| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
PDD00017273 targets PARG (poly(ADP-ribose) glycohydrolase), an enzyme that catalyzes the hydrolysis of O-glycosidic linkages of ADP-ribose polymers, reversing the effects of poly(ADP-ribose) polymerases (PARPs). PARG has been shown to be involved in the repair of single-strand DNA breaks. By inhibiting PARG, PDD00017273 disrupts the DNA damage response pathway, making it particularly useful in cancer research for studying DNA repair mechanisms and developing combination therapies with genotoxic agents.
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| ln Vitro |
PDD 00017273 is a powerful PARG reagent with an IC50 of 26 nM and a KD of 1.45 nM. For five typical cytochrome P450 enzymes, PDD 00017273 (10 μM) does not inhibit. In addition to inhibiting NAD/H through PARG after DNA damage, PDD 00017273 (30 μM) increases the intensity of phosphorylated H2AX (γH2AX). When it comes to MDA-MB-436 cells labeled with 5396 + 1G>A in BRCA1, PDD 00017273 exhibits minimal activity, but it inhibits ZR-75-1 cells labeled with wild-type BRCA1 and BRCA2 [1]. The breakdown of PAR medium in MCF7 cells is inhibited by PDD 00017273 (0.3 μM). Additionally, BARD1, BRCA2, PALB2, FAM175A, and BRCA1 latency are decreased by PDD 00017273 (0.3 μM). Inducing DNA damage that must be repaired by homologous recombination (HR) and stopping replication forks are the effects of PDD 00017273 [2].
In vitro, PDD00017273 potently inhibits PARG enzymatic activity with an IC50 of 26 nM. The compound exhibits >350-fold selectivity for PARG over a panel of ion channels, enzymes, and receptors, including PARP1 and ARH3. It is cell-permeable and has been shown to specifically kill cells defective in certain homologous recombination proteins such as BRCA1/2. PDD00017273 is used in cancer research to study DNA repair mechanisms and as a radiosensitizing agent. |
| ln Vivo |
In vivo, PDD00017273 has demonstrated antitumor activity in preclinical models. The compound is used in cancer research to study DNA repair mechanisms and develop combination therapies with genotoxic agents. Studies have shown that PARG inhibition by PDD00017273 can sensitize tumors to radiation and chemotherapeutic agents, particularly in tumors with DNA repair deficiencies or p53 mutations. Further in vivo studies are ongoing to evaluate its therapeutic potential.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for PDD00017273 measures PARG enzymatic activity using purified PARG enzyme and a suitable substrate (e.g., ADP-ribose polymers or fluorescently labeled substrates). The assay is performed in optimized buffer systems at 37°C, and the reaction is terminated by the addition of stop solution. Product formation is quantified by fluorescence, absorbance, or HPLC. IC50 values are calculated from dose-response curves by fitting data to a four-parameter logistic equation. Selectivity is assessed against a panel of related enzymes including PARP1 and ARH3.
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| Cell Assay |
In vitro cellular studies are conducted using cancer cell lines, particularly those with DNA repair deficiencies or p53 mutations. Cells are treated with PDD00017273 at various concentrations (typically nanomolar to micromolar) for defined time periods. Cell viability is assessed using CellTiter-Glo or MTT assays. DNA damage and repair are evaluated by measuring γH2AX foci formation, comet assays, or analysis of PAR polymer accumulation. Combination studies with radiation or genotoxic agents are performed to evaluate potential synergistic effects.
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| Animal Protocol |
In vivo animal experiments are performed in mouse xenograft models using human cancer cell lines. Tumor-bearing mice are administered PDD00017273 via oral gavage or intraperitoneal injection at various doses. Tumor volume is measured over time, and endpoints include tumor growth inhibition, survival, and biomarkers of PARG inhibition (e.g., PAR polymer levels). Pharmacodynamic studies evaluate target engagement and pathway modulation in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PDD00017273 include cell permeability and solubility in DMSO (10 mg/mL or 100 mg/mL). The compound is insoluble in water and ethanol. It has a molecular weight of 514.62 g/mol and appears as a white to beige powder. Storage at 2-8°C is recommended. The compound should be protected from moisture, and DMSO stock solutions should be used fresh to maintain solubility.
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| Toxicity/Toxicokinetics |
Toxicological data for PDD00017273 are limited to preclinical studies. The compound is for research use only and not intended for human therapeutic applications. Standard safety precautions should be followed when handling the compound. No significant acute toxicity has been reported at effective doses in animal studies. Long-term toxicity and carcinogenicity studies have not been conducted.
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| References |
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| Additional Infomation |
PDD00017273 is also known as PDD 00017273. It is a potent and selective PARG inhibitor with an IC50 of 26 nM and >350-fold selectivity over PARP1 and ARH3. The compound is used in cancer research, particularly for studying DNA repair mechanisms and developing combination therapies with genotoxic agents. It is supplied as a powder with ≥98% purity and is available in various sizes for research purposes.
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| Molecular Formula |
C23H26N6O4S2
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|---|---|
| Molecular Weight |
514.6203
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| Exact Mass |
514.146
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| CAS # |
1945950-21-9
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| Related CAS # |
1945950-21-9;
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| PubChem CID |
121398766
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
954
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC2=C(C(N(CC3=CN=C(C)S3)C(N2CC2=CC(C)=NN2C)=O)=O)C=1)(NC1(C)CC1)(=O)=O
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| InChi Key |
IFWUBRBMMNTBRZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H26N6O4S2/c1-14-9-16(27(4)25-14)12-28-20-6-5-18(35(32,33)26-23(3)7-8-23)10-19(20)21(30)29(22(28)31)13-17-11-24-15(2)34-17/h5-6,9-11,26H,7-8,12-13H2,1-4H3
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| Chemical Name |
1-[(1,3-Dimethyl-1H-pyrazol-5-yl)methyl]-1,2,3,4-tetrahydro-N-(1-methylcyclopropyl)-3-[(2-methyl-5-thiazolyl)methyl]-2,4-dioxo-6-quinazolinesulfonamide
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| Synonyms |
PDD-00017273 PDD 00017273 PDD00017273 PDD-17273 PDD 17273 PDD 17273
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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) |
DMSO : ~25 mg/mL (~48.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.86 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 25.0 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: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9432 mL | 9.7159 mL | 19.4318 mL | |
| 5 mM | 0.3886 mL | 1.9432 mL | 3.8864 mL | |
| 10 mM | 0.1943 mL | 0.9716 mL | 1.9432 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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