DPQ

Product NameDPQ
CAS129075-73-6
MFC18H26N2O2
MW302.41
EINECS
MOL File129075-73-6.mol

Chemical Properties

Melting point	107-109°
Boiling point	528.8±50.0 °C(Predicted)
Density	1.096±0.06 g/cm3(Predicted)
storage temp.	2-8°C
solubility	DMSO: Soluble
form	solid
pka	14.54±0.20(Predicted)
color	White to off-white
biological source	synthetic (organic)
InChI	1S/C18H26N2O2/c21-18-16-7-6-8-17(15(16)9-10-19-18)22-14-5-4-13-20-11-2-1-3-12-20/h6-8H,1-5,9-14H2,(H,19,21)
InChIKey	RVOUDNBEIXGHJY-UHFFFAOYSA-N
SMILES	N3(CCCCC3)CCCCOc1c2c(ccc1)C(=O)NCC2

Safety Information

Hazard Codes	Xi
Risk Statements	36/37/38
Safety Statements	26-36
WGK Germany	3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Description

The poly(ADP-ribose) polymerases (PARPs) form a family of enzymes with roles in DNA repair and apoptosis, particularly in response to reactive oxygen and nitrogen species. DPQ is a potent inhibitor of PARPs, inhibiting PARP1 with an IC₅₀ value of 40 nM. It is approximately 10-fold less potent against PARP2. DPQ can be used in either cells or in animals.

Uses

DPQ has been used as a PARP1 (poly(ADP-ribose) polymerase 1) inhibitor in in vivo studies to determine the loss of γ-H2AX (H2A histone family member X) upon irradiation.

Uses

Reagent for inhibition of PARP.

Uses

3,4-Dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone is a potent inhibitor of poly(ADP-ribose) polymerases, a family of enzymes that plays a crucial role in DNA repair and apoptosis in respons e to reactive oxygen and nitrogen species.

Biochem/physiol Actions

3,4-Dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) is known to decrease the PARP 1 (poly(ADP-ribose) polymerase 1) mediated apoptosis under the influence of ischemia. It is considered as more effective inhibitor than the traditionally used PARP1 inhibitor 3-aminobenzamide.

in vivo

DPQ (10 mg/kg; intraperitoneal injection; single dose; 6 h) significantly attenuates lung inflammation, neutrophil infiltration, and vascular leakage in LPS-induced acute lung injury model of C57BL/6 mice, inhibiting NF-κB pathway activation^[2].
DPQ (10 mg/kg; intraperitoneal injection; single dose; 4 weeks) improves cardiac function and reduced apoptosis and oxidative stress in myocardial infarction model of Wistar rats^[3].

Animal Model:	LPS-Induced Acute Lung Injury Model in C57BL/6 mice (male, 8-10 weeks old)
Dosage:	10 μg/kg (dissolved in 0.01% DMSO (PBS)
Administration:	Intraperitoneal injection, 30 min after LPS chanllenge (7.5 mg/kg; ip; single dose)
Result:	Reduced neutrophil infiltration (50% decrease), MPO activity (40% decrease), and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in lungs. Restored vascular permeability (Evans blue extravasation reduced by 35%), and inhibited apoptotic cell death (TUNEL-positive cells decreased by 45%). Suppressed NF-κB activation with reduced IkB-α degradation and p65 phosphorylation.

Animal Model:	Myocardial Infarction model in Wistar rats (male, 4 months old) via coronary artery ligation^[3]
Dosage:	10 mg/kg (dissolved in DMSO)
Administration:	Intraperitoneal injection, single dose immediately after MI induction
Result:	Improved cardiac function (FS increased by 25%, EDD/ESD reduced by 15%), decreased apoptotic cardiomyocytes (TUNEL-positive cells reduced by 40%), and suppressed cleaved caspase-3 and PARP1 expression. Oxidative stress markers (O^2-, nitrotyrosine) were reduced by 30-40% in infarcted myocardium.

IC 50

PARP-1

storage

+4°C

References

[1] D DAVAR. Role of PARP inhibitors in cancer biology and therapy.[J]. Current medicinal chemistry, 2012, 19 23: 3907-3921. DOI: 10.2174/092986712802002464
[2] MARLENE T MATHEWS Bradford C B. PARP-1 inhibition prevents oxidative and nitrosative stress-induced endothelial cell death via transactivation of the VEGF receptor 2.[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2008, 28 4: 711-717. DOI: 10.1161/atvbaha.107.156406
[3] GABRIELE COSTANTINO. Modeling of Poly(ADP-ribose)polymerase (PARP) Inhibitors. Docking of Ligands and Quantitative StructureActivity Relationship Analysis[J]. Journal of Medicinal Chemistry, 2001, 44 23: 3786-3794. DOI: 10.1021/jm010116l
[4] TOBIAS ELTZE. Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors.[J]. ACS Applied Electronic Materials, 2008: 1587-1598. DOI: 10.1124/mol.108.048751
[5] ELENA FONFRIA. TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase[J]. British Journal of Pharmacology, 2009, 143 1: 186-192. DOI: 10.1038/sj.bjp.0705914
[6] L. GIOVANNELLI. Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors[J]. Journal of Cerebral Blood Flow & Metabolism, 2002, 39 1 1: 697-704. DOI: 10.1097/00004647-200206000-00008

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