Olaparib (AZD2281)

製品コードS1060 バッチS106025

印刷

化学情報

Chemical Structure Synonyms Ku-0059436 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H23FN4O3
分子量 434.46 CAS No. 763113-22-0
Solubility (25°C)* 体外 DMSO 87 mg/mL (200.24 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
10%DMSO 90%Corn oil
10.0mg/ml Taking the 1 mL working solution as an example, add 100 μL of 100 mg/ml clear DMSO stock solution to 900 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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 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。
in vitro

Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib 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] Olaparib 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

Combining with temozolomide, Olaparib (10 mg/kg, p.o.) significantly suppresses tumor growth in SW620 xenografts. [1] Olaparib 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. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. [3] Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib 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)
To columns 1 through 10, 1 μL of Olaparib (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 is measured by clonogenic assay. Olaparib 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 Olaparib 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.
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

カスタマーフィードバック

Data from [Data independently produced by Cancer Res, 2014, 74(21), 5948-54]

Data from [Data independently produced by Medicine (Baltimore), 2014, 93(28), e294]

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：

Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 10.1038/s41586-024-07217-2] PubMed: 38509368
PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends [ Cell, 2024, 187(4):945-961.e18] PubMed: 38320550
FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress [ Nat Commun, 2024, 15(1):866] PubMed: 38286805
Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer [ Cell Rep Med, 2024, 5(2):101396] PubMed: 38290515
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94] PubMed: 38316520
Poly(ADP-ribosyl)ation of TIMELESS limits DNA replication stress and promotes stalled fork protection [ Cell Rep, 2024, 43(3):113845] PubMed: 38393943
The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability [ Cell Rep, 2024, 43(2):113779] PubMed: 38358891
CASK Mediates Oxidative Stress-Induced Microglial Apoptosis-Inducing Factor-Independent Parthanatos Cell Death via Promoting PARP-1 Hyperactivation and Mitochondrial Dysfunction [ Antioxidants (Basel), 2024, 13(3)343] PubMed: 38539876
PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation [ Cells, 2024, 13(2)159] PubMed: 38247850
Type III secretion system effector YfiD inhibits the activation of host poly(ADP-ribose) polymerase-1 to promote bacterial infection [ Commun Biol, 2024, 7(1):162] PubMed: 38332126

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。

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