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受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
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Synonyms | Ku-0059436 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C24H23FN4O3 |
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| 分子量 | 434.46 | CAS No. | 763113-22-0 | |
| Solubility (25°C)* | 体外 | DMSO | 125 mg/mL (287.71 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | オラパリブ (Olaparib (AZD2281, KU0059436)) は選択的 PARP1/2 阻害剤であり、cell-free assay における IC50 はそれぞれ 5 nM および 1 nM です。タンキラーゼ-1 (Tankyrase-1) に対しては 1/300 の効果を示します。オラパリブは BRCA に変異をきたした細胞において、マイトファジー (mitophagy) に関連した顕著なオートファジー (mitophagy) を誘発します。 |
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| in vitro | Olaparib (AZD2281) would act against BRCA1 or BRCA2 mutations and is not sensitive to tankyrase-1 (IC50 >1 μM). It could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. This compound is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). [1] It is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways. [2] |
| in vivo | Olaparib (AZD2281) (10 mg/kg, p.o.) in Combination significantly suppresses tumor growth in SW620 xenografts. [1] It shows great response to Brca1-/-;p53-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad-/-;p53-/- mammary tumors. This compound even does not show dose-limiting toxicity in tumor-bearing mice. [3] It has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, it shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors. [4] |
| 特徴 | A potent PARP inhibitor (currently in late stage clinical trials). |
プロトコル(参考用のみ)
| キナーゼアッセイ | FlashPlate assay (96-well screening assay) | |
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| To columns 1 through 10, 1 μL of Olaparib (AZD2281) (in DMSO) is added, and 1 μL DMSO only is added to the positive (POS) and negative (NEG) control wells (columns 11 and 12, respectively) of a pretreated FlashPlate. PARP-1 is diluted 1:40 in buffer (buffer B: 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl2,50 mM KCl, 1 mM DTT, 0.01% NP-40 (v/v), pH 7.6) and 40 μL added to all 96 wells (final PARP-1 concentration in the assay is ~1 ng/μL). The plate is sealed and shaken at RT for 15 min. Following this, 10 μL of positive reaction mix (0.2 ng/μL of double-stranded oligonucleotide [M3/M4] DNA per well, 5 μM of NAD+ final assay concentration, and 0.075 μCi 3H-NAD+ per well) is added to the appropriate wells (columns 1-11). The negative reaction mix, lacking the DNA oligonucleotide, is added to column 12 (with the mean negative control value used as the background). The plate is resealed and shaken for a further 60 min at RT to allow the reaction to continue. Then, 50 μL of ice-cold acetic acid (30%) is added to each well to stop the reaction, and the plate is sealed and shaken for a further 60 min at RT. Tritiated signal bound to the FlashPlate is then determined in counts per minute (CPM) using the TopCount plate reader. | ||
| 細胞アッセイ | 細胞株 | Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D |
| 濃度 | 1-300 nM | |
| 反応時間 | 7-14 days | |
| 実験の流れ | The cytotoxicity of Olaparib (AZD2281) is measured by clonogenic assay. It is dissolved in DMSO and diluted by culture media before use. The cells are seeded in six well plates and left to attach overnight. Then this compound is added at various concentrations and the cells are incubated for 7-14 days. After that the surviving colonies are counted for calculating the IC50. |
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| 動物実験 | 動物モデル | Brca1-/-;p53-/- mammary tumors are generated in K14cre;Brca1F/F;p53F/F mice. |
| 投薬量 | 50 mg/kg | |
| 投与方法 | Administered via i.p. injection at 10 μL/g of body weight | |
参考
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カスタマーフィードバック
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Data from [Data independently produced by Cancer Res, 2014, 74(21), 5948-54]
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Data from [Data independently produced by Medicine (Baltimore), 2014, 93(28), e294]
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Data from [J Exp Clin Cancer Res, 2013, 32(1), 95]
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：
| KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer [ Cancer Cell, 2025, 43(8):1530-1548.e9] | PubMed: 40645185 |
| Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups [ Cancer Cell, 2025, 43(4):776-796.e14] | PubMed: 40185092 |
| Jab1 regulates HRR mRNA stability to modulate PARP inhibitor sensitivity in triple-negative breast cancer [ Mol Cancer, 2025, 24(1):217] | PubMed: 40819058 |
| The transcriptomic architecture of common cancers reflects synthetic lethal interactions [ Nat Genet, 2025, 57(3):522-529] | PubMed: 40033056 |
| The molecular and functional landscape of resistance to FOLFIRI chemotherapy in metastatic colorectal cancer [ Cancer Discov, 2025, 10.1158/2159-8290.CD-24-0556] | PubMed: 40981426 |
| Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer [ Nat Cancer, 2025, 10.1038/s43018-025-00960-z] | PubMed: 40301653 |
| Insufficient telomeric DNA damage response promotes chromosomal instability in aged oocytes [ Sci Bull (Beijing), 2025, S2095-9273(25)00865-5] | PubMed: 40930920 |
| OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts [ Nat Commun, 2025, 16(1):893] | PubMed: 39837827 |
| EXO1 as a therapeutic target for Fanconi Anaemia, ZRSR2 and BRCA1-A complex deficient cancers [ Nat Commun, 2025, 16(1):8476] | PubMed: 41006228 |
| Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers [ Nat Commun, 2025, 16(1):6972] | PubMed: 40730818 |
長期の保管のために-20°Cの下で製品を保ってください。
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。