| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
| Targets |
PARP-1 ( IC50 = 0.20 μM ); PARP-2 ( IC50 = 0.24 μM )
DR-2313 targets poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2, nuclear enzymes that play a central role in DNA repair. Upon detection of DNA damage, PARP-1 and PARP-2 catalyze the synthesis of poly(ADP-ribose) (PAR) chains on target proteins, a process that is essential for recruiting DNA repair machinery. However, excessive activation of PARP in response to severe DNA damage, such as that occurring during ischemia, can deplete cellular NAD⁺ and ATP, leading to cell death. By competitively binding to the active site of PARP, DR-2313 inhibits this enzymatic activity and blocks the excessive PARP activation that drives neuronal cell death. |
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| ln Vitro |
DR2313 (0.016-16.4 μM; 30 min) inhibits the poly(ADP-ribosyl)ation reaction with a Ki of 0.23 μM, in rat brain nuclear extracts[1].
DR2313 demonstrates a superior inhibition of poly(ADP-ribosyl)ation in rat brain nuclear extracts (IC50=0.20 μM) compared to DPQ (0.96 μM), DIQ (2.96 μM), PND (0.56 μM), and 3AB (35.4 μM)[1]. DR2313 (1-100 μM; 10 min) exhibits a weak inhibition of mono(ADP-ribosyl) ation (IC50=59 μM) in a concentration-dependent manner (IC50=59 μM)[1]. DR2313 (0.1–30 μM; pretreated for 30 min) lessens the excessive formation of poly(ADP-ribose) and cell death caused by glutamate (1 mM; 30 min) or hydrogen peroxide (500 μM; 4 h)[1]. In vitro, DR-2313 demonstrates potent inhibition of PARP activity. It inhibits the poly(ADP-ribosyl)ation reaction in rat brain nuclear extracts with a Ki of 0.23 μM and an IC50 of 0.20 μM, showing superior potency compared to other PARP inhibitors like DPQ (0.96 μM), DIQ (2.96 μM), and 3AB (35.4 μM). The compound exhibits a weak inhibition of mono(ADP-ribosyl)ation (IC50 = 59 μM), confirming its selectivity for PARP over other ADP-ribosyltransferases. DR-2313 lessens the excessive formation of PAR and cell death caused by glutamate or hydrogen peroxide in cellular models of neurotoxicity. |
| ln Vivo |
DR2313 (3-10 mg/kg i.v. bolus or infusion for 6 h) significantly reduces the cortical infarct volume in both permanent and transient focal ischemia models in rats[1].
In vivo, DR-2313 demonstrates significant neuroprotective effects. In rat models of focal cerebral ischemia, intravenous administration of DR-2313 (3-10 mg/kg as a bolus or 6-hour infusion) significantly reduces cortical infarct volume in both permanent and transient middle cerebral artery occlusion (MCAO) models. This reduction in infarct size confirms the compound's ability to cross the blood-brain barrier and exert its protective effect in the brain. The neuroprotection is attributed to the inhibition of PARP-mediated cell death pathways in the ischemic tissue. |
| Enzyme Assay |
The inhibitory activity of DR-2313 against PARP-1 and PARP-2 is assessed using in vitro enzyme assays. In a cell-free system, recombinant PARP-1 or PARP-2 enzymes are incubated with a DNA substrate, NAD⁺, and varying concentrations of DR-2313. The reaction is monitored by measuring the incorporation of biotinylated-NAD⁺ into PAR polymers, and the IC50 is calculated from the dose-response curve. The competitive nature of the inhibition can be confirmed by varying the concentration of the NAD⁺ substrate.
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| Cell Assay |
The cellular activity of DR-2313 is evaluated in neuronal cell cultures or brain slices. Cells are treated with the compound prior to exposure to neurotoxic insults, such as glutamate or hydrogen peroxide. The extent of PAR formation, cell viability, and markers of cell death are then measured. For instance, DR-2313 has been shown to reduce PAR formation and cell death caused by glutamate in these models, confirming its cellular neuroprotective activity.
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| Animal Protocol |
Male Wistar rats (220-300 g) with permanent MCA occlusions (pMCAos) and transient MCA occlusions (tMCAos)
3, 10 mg/kg I.v. bolus and i.v. infusion for 6 h beginning 5 min before the onset of ischemia In animal studies, DR-2313 is typically administered intravenously (i.v.) to rats or mice. In models of focal cerebral ischemia, the compound is given as an i.v. bolus or as a continuous infusion beginning shortly before the onset of ischemia. Doses typically range from 1 to 10 mg/kg. The primary endpoint is the reduction in infarct volume, which is assessed by histological staining of brain sections. Plasma and brain concentrations of the compound are measured to confirm its brain penetration and to establish pharmacokinetic-pharmacodynamic relationships. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of DR-2313 are not extensively detailed in the provided literature. However, it is described as a brain-penetrant inhibitor, indicating that it is able to cross the blood-brain barrier. Following intravenous administration, its half-life and volume of distribution would be characteristic of a small molecule. Its clearance is likely via renal and hepatic routes. The compound's ability to achieve therapeutic concentrations in the brain is a key feature for its neuroprotective applications.
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| Toxicity/Toxicokinetics |
Toxicology data for DR-2313 is not provided in the available literature. As a research compound, its safety profile has not been established in formal toxicology studies. However, its use in animal models of stroke at neuroprotective doses suggests it is tolerated at those concentrations. Potential off-target effects and toxicity would need to be evaluated if it were to be developed for clinical use. The compound is for research use only and not for human therapeutic applications.
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| References |
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| Additional Infomation |
DR-2313 (CAS: 284028-90-6) is a well-characterized, brain-penetrant PARP-1/2 inhibitor used extensively in neuroscience research. Its IC50 values of 0.20 μM and 0.24 μM for PARP-1 and PARP-2, respectively, and its competitive mechanism of action make it a standard tool for studying PARP-mediated cell death. Its demonstrated neuroprotective efficacy in rodent models of stroke has solidified its role as a key compound for investigating the therapeutic potential of PARP inhibition for cerebral ischemia and other neurological disorders.
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| Molecular Formula |
C8H10N2OS
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|---|---|
| Molecular Weight |
182.2428
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| Exact Mass |
182.051
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| Elemental Analysis |
C, 52.73; H, 5.53; N, 15.37; O, 8.78; S, 17.59
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| CAS # |
284028-90-6
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| PubChem CID |
135522417
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
349.3±52.0 °C at 760 mmHg
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| Flash Point |
165.0±30.7 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.714
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| LogP |
0.66
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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 |
0
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| Heavy Atom Count |
12
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| Complexity |
293
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC(=C2CSCCC2=N1)O
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| InChi Key |
HRYKZAKEAVZGJD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H10N2OS/c1-5-9-7-2-3-12-4-6(7)8(11)10-5/h2-4H2,1H3,(H,9,10,11)
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| Chemical Name |
2-methyl-3,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one
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| Synonyms |
PARP Inhibitor XI; DR2313; DR-2313; DR 2313
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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 requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
Water : ~36 mg/mL (~197.5 mM)
Ethanol : ~5 mg/mL (~27.4 mM) DMSO : 12.5~18 mg/mL (68.6~98.8 mM) |
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.4873 mL | 27.4363 mL | 54.8727 mL | |
| 5 mM | 1.0975 mL | 5.4873 mL | 10.9745 mL | |
| 10 mM | 0.5487 mL | 2.7436 mL | 5.4873 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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