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    InvivoChem Cat #: V0202
    CAS #: 1048371-03-4Purity ≥98%

    Description: UPF 1069 (UPF-1069), an isoquinolinone derivative, is a novel, potent and selective inhibitor of poly-(ADP-ribose) polymerase 2 (PARP-2) with potential neurprotective and anti-ischemic effects in vivo. It inhibits PARP-2 with  IC50s of 8 and 0.3 μM for PARP-1 and PARP-2, respectively. It is able to induce apoptosis and reduce PAR formation both in recombinant enzyme preparations and in nuclear extracts from PARP-1-/- fibroblasts. UPF 1069 is more selective for PARP-2 than PARP-1 (IC50 = 8 μmol/L). It has been used to investigate the role of PARP-1 and PARP-2 in post-ischaemic brain damage.

    ReferencesBr J Pharmacol. 2009 Jul;157(5):854-62.

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    Molecular Weight (MW)279.29
    CAS No.1048371-03-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 56 mg/mL (200.5 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL 
    Synonyms & Other info

    Synonym: UPF-1069, UPF 1069, UPF1069

    Chemical Name: 5-(2-oxo-2-phenylethoxy)isoquinolin-1(2H)-one


    InChi Code: InChI=1S/C17H13NO3/c19-15(12-5-2-1-3-6-12)11-21-16-8-4-7-14-13(16)9-10-18-17(14)20/h1-10H,11H2,(H,18,20)


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    In Vitro

    In vitro activity: PF 1069 (Compound 55) is a PARP inhibitor, with IC50s of 8 and 0.3 μM for PARP-1 and PARP-2, respectively. UPF 1069 (1 µM) reduces the residual PARP activity by approximately 80% of PARP-1-deficient fibroblasts, but only slightly inhibits the enzymic activity in wild-type fibroblasts. UPF 1069 (0.1-1 µM) markedly enhances CA1 hippocampal damage. UPF 1069 (10 µM) also exacerbates oxygen-glucose deprivation (OGD) damage in organotypic hippocampal slices. However, UPF 1069 alleviates the damage cuased by OGD in mixed cortical cell cultures, shows a potent neuroprotective activity both at a concentration (1 µM) selectively acting on PARP-2 and at a concentration (10 µM) inhibiting both PARP-1 and PARP-2 activities.

    Kinase Assay: PARP activity is evaluated by utilizing commercially available recombinant bovine PARP-1 and mouse PARP-2. Briefly, the enzymatic reaction is carried out in 100 µL of 50 mM Tris-HCl (pH 8.0) containing 5 mM MgCl2, 2 mM dithiothreitol, 10 µg sonicated calf thymus DNA, 0.2 µCi [adenine-2,8-3H]NAD and recombinant enzyme PARP-1 or PARP-2 (0.03 U per sample). Different concentrations of the putative inhibitors are added, and the mixture is incubated for 1 h at 37°C. The reaction is terminated by adding 1 mL of 10% trichloroacetic acid (w/v) and centrifuged. Pellets are then washed twice with 1 mL of H2O and resuspended in 1 mL of 0.1 M NaOH. The radioactivity incorporated from [adenine-2,8-3H]NAD into proteins is evaluated by liquid scintillation spectrometry.

    In VivoIn organotypic hippocampal slices, PARP-2 inhibition with UPF-1069 (0.01-1 mM) causes a concentration-dependent exacerbation (up to 155%) of oxygen-glucose deprivation (OGD)-induced CA1 pyramidal cell death. Higher concentrations, acting on both PARP-1 and PARP-2, have no effect on OGD injury. In mouse mixed cortical cells exposed to OGD, UPF-1069 (1-10 mM) significantly reduces post-ischaemic damage.
    Animal modelMouse
    Formulation & Dosage0.01-1 mM

    Br J Pharmacol. 2009 Jul;157(5):854-62.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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