DR 2313

Names

[ Name ]:
DR 2313

[Synonym ]:
2-Methyl-1,5,7,8-tetrahydro-4H-thiopyrano[4,3-d]pyrimidin-4-one
3,5,7,8-Tetrahydro-2-methyl-4H-thiopyrano[4,3-d]pyrimidin-4-one
2-methyl-3,5,7,8-tetrahydrothiopyrano(4,3-d)pyrimidine-4-one
7,8-Dihydro-2-methyl-1H-thiopyrano[4,3-d]pyrimidin-4(5H)-one
4H-Thiopyrano[4,3-d]pyrimidin-4-one, 1,5,7,8-tetrahydro-2-methyl-
DR 2313
1,5,7,8-TETRAHYDRO-2-METHYL-4H-THIOPYRANO[4,3-D]PYRIMIDIN-4-ONE
2-Methyl-1-sulfanyl-1H,4H,5H,7H,8H-pyrano[4,3-d]pyriMidin-4-one
3,5,7,8-tetrahydro-2-methyl-4h-thiopyrano(4,3-d)pyrimidin-4-one

Biological Activity

[Description]:

DR2313 is a potent, selective, competitive 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. DR2313 exhibits neuroprotective effects on ischemic injuries in vitro and in vivo[1][2].

[Related Catalog]:

Signaling Pathways >> Epigenetics >> PARP

Research Areas >> Neurological Disease

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

[Target]

PARP-1:0.20 μM (IC50)

PARP-2:0.24 μM (IC50)

[In Vitro]

DR2313 (0.016-16.4 μM; 30 min) inhibits poly(ADP-ribosyl)ation reaction in nuclear extracts of rat brain, with a Ki of 0.23 μM[1]. DR2313 shows more powerful inhibition of the poly(ADP-ribosyl)ation in the nuclear extracts of the rat brain (IC50=0.20 μM) than 3AB (35.4 μM), PND (0.56 μM), DIQ (2.96 μM), and DPQ (0.96 μM)[1]. DR2313 (1-100 μM; 10 min) shows a weak inhibition of the mono(ADP-ribosyl)ation in a concentration-dependent manner (IC50=59 μM)[1]. DR2313 (0.1-30 μM; pretreated for 30 min) reduces hydrogen peroxide (500 μM; 4 h) or glutamate (1 mM; 30 min) induced excessive formation of poly(ADP-ribose) and cell death[1].

[In 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 Model: Male Wistar rats (220-300 g) with permanent MCA occlusions (pMCAos) and transient MCA occlusions (tMCAos)[1] Dosage: 3, 10 mg/kg Administration: I.v. bolus and i.v. infusion for 6 h beginning 5 min before the onset of ischemia Result: Reduced the infarct volume in a dose-dependent manner in pMCAo and tMCAo model.

[References]

[1]. Nakajima H, et, al. 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]. Xu Z, et, al. 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.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
349.3±52.0 °C at 760 mmHg

[ Molecular Formula ]:
C₈H₁₀N₂OS

[ Molecular Weight ]:
182.243

[ Flash Point ]:
165.0±30.7 °C

[ Exact Mass ]:
182.051376

[ PSA ]:
71.05000

[ LogP ]:
0.66

[ Vapour Pressure ]:
0.0±0.8 mmHg at 25°C

[ Index of Refraction ]:
1.714

[ Storage condition ]:
2~8°C

MSDS

Click to get detail MSDS

Safety Information

[ Hazard Codes ]:
Xn

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2934999090

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%