UPF 1069

製品コードS8038 バッチS803802

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H13NO3
分子量 279.29 CAS No. 1048371-03-4
Solubility (25°C)* 体外 DMSO 56 mg/mL (200.5 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 UPF 1069 is a selective PARP2 inhibitor with IC50 of 0.3 μM. It is ~27-fold selective against PARP1.
in vitro UPF 1069 is a selective PARP2 inhibitor with IC50 of 0.3 μM while inhibiting PARP1 with IC50 of 8 μM. [1]
in vivo In 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. [1]
特徴 The most selective PARP2 inhibitor available to date.

プロトコル(参考用のみ)

キナーゼアッセイ PARP-1 and PARP-2 activity assays
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 mL of 50 mM Tris-HCl (pH 8.0) containing 5 mM MgCl2, 2 mM dithiothreitol, 10 mg sonicatedcalf thymus DNA, 0.2 mCi [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℃. 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. Nuclear extracts for PARP activity assay are prepared from PARP-1-/- and PARP-1+/+ mouse fibroblasts as previouslydescribed. Briefly, immortalized fibroblasts from PARP-1-/- and PARP-1+/+ mice are grown in DMEM supplemented with 2 mM glutamine, 10% bovine serum and antibiotics at 37℃. Nuclear extracts are prepared as follows: 10 cm confluent plates are scraped in 1 mL of homogenization buffer composed of 75 mM sucrose, 225 mM mannitol and 5 mM Tris, pH 7.4 plus 10 mL protease inhibitor cocktail. The cell suspension is homogenized with a Teflon pestle, and the mixture is centrifuged at 600 × g for 5 min at 4℃. The crude nuclear pellet is washed and resuspended in 1 mL of PARP assay buffer (5 mM MgCl2, 2 mM DTT, 50 mM Tris, pH 8) containing 100 mM N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) to fully activate PARP activity. Samples containing 100 mL of the resuspended nuclear pellet are incubated for 60 min at 37℃ in the presence of 35.5 nM 3H-NAD. The reaction is stopped with 1 mL of 10% trichloroacetic acid (w/v), and the mixture is centrifuged at 12 000 × g for 10 min at 4℃. The reaction is terminated by the addition of 1 mL of 10% trichloroacetic acid (w/v), and radioactivity of the suspension is measured by liquid scintillation spectrometry.
動物実験 動物モデル Rats deprived of hippocampi.
投薬量 0.01-1 mM
投与方法

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The interplay of TARG1 and PARG protects against genomic instability [ Cell Rep, 2023, 42(9):113113] PubMed: 37676774
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] PubMed: 37066268
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] PubMed: 37066268
Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51 [ Cell Death Differ, 2021, 10.1038/s41418-020-00733-4] PubMed: 33531658
Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status. [ J Clin Med, 2020, 30;9(4)] PubMed: 32235451
Enabling drug discovery for the PARP protein family through the detection of mono-ADP-ribosylation [ Biochem Pharmacol, 2019, 10.1016/j.bcp.2019.05.007] PubMed: 31075269
DNA‑PKcs PARylation regulates DNA‑PK kinase activity in the DNA damage response. [ Mol Med Rep, 2019, 20(4):3609-3616] PubMed: 31485633
Inhibition of Parp1 by BMN673 Effectively Sensitizes Cells to Radiotherapy by Upsetting the Balance of Repair Pathways Processing DNA Double-Strand Breaks [ Mol Cancer Ther, 2018, 17(10):2206-2216] PubMed: 29970481
Dual Inhibitors of PARPs and ROCKs. [ ACS Omega, 2018, 3(10):12707-12712] PubMed: 30411017

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人間や獣医の診断であるか治療的な使用のためにでない。

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