DR2313 is a novel and brain-penetrant inhibitor of poly(ADP-ribose) polymerase (PARP), with IC50s of 0.20 μM and 0.24 μM for PARP-1 and PARP-2, respectively. In vitro and in vivo, DR2313 demonstrates neuroprotective effects on ischemic injuries.

Physicochemical Properties

Molecular Formula	C8H10N2OS
Molecular Weight	182.2428
Exact Mass	182.051
Elemental Analysis	C, 52.73; H, 5.53; N, 15.37; O, 8.78; S, 17.59
CAS #	284028-90-6
PubChem CID	135522417
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	349.3±52.0 °C at 760 mmHg
Flash Point	165.0±30.7 °C
Vapour Pressure	0.0±0.8 mmHg at 25°C
Index of Refraction	1.714
LogP	0.66
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	0
Heavy Atom Count	12
Complexity	293
Defined Atom Stereocenter Count	0
SMILES	CC1=NC(=C2CSCCC2=N1)O
InChi Key	HRYKZAKEAVZGJD-UHFFFAOYSA-N
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)
Chemical Name	2-methyl-3,5,7,8-tetrahydrothiopyrano[4,3-d]pyrimidin-4-one
Synonyms	PARP Inhibitor XI; DR2313; DR-2313; DR 2313
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	PARP-1 ( IC50 = 0.20 μM ); PARP-2 ( IC50 = 0.24 μM )
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].
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].
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
References	[1]. A newly synthesized poly(ADP-ribose) polymerase inhibitor, DR2313 [2-methyl-3,5,7,8-tetrahydrothiopyrano[4,3-d]-pyrimidine-4-one]: pharmacological profiles, neuroprotective effects, and therapeutic time window in cerebral ischemia in rats. J Pharmacol Exp Ther . 2005 Feb;312(2):472-81. [2]. Endonuclease G does not play an obligatory role in poly(ADP-ribose) polymerase-dependent cell death after transient focal cerebral ischemia. Am J Physiol Regul Integr Comp Physiol. 2010 Jul;299(1):R215-21.

Solubility Data

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)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.