奥拉帕尼作用机制 - Medchemexpress - MCE中国

Product Data?SheetOlaparibCat. No.:CAS No.:分?式:分?量:作?靶点:作?通路:储存?式:HY-10162763113-22-0C??H??FN?O?434.46PARP; Autophagy; MitophagyCell Cycle/DNA Damage; Epigenetics; AutophagyPowderIn solvent-20°C4°C-80°C-20°C3 years2 years6 months1 monthInhibitors?Agonists?Screening Libraries溶解性数据体外实验DMSO : ≥ 33.33 mg/mL (76.72 mM)* \Mass1 mg5 mg10 mgSolventConcentration制备储备液1 mM5 mM10 mM2.3017 mL0.4603 mL0.2302 mL11.5085 mL2.3017 mL1.1509 mL23.0171 mL4.6034 mL2.3017 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；?旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存?式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个?内使?，-20°C 储存时，请在 1 个?内使?。体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照 In Vitro ?式配制澄清的储备液，再依次添加助溶剂： 为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的?作液，建议您现?现配，当天使?； 以下溶剂前显?的百分?是指该溶剂在您配制终溶液中的体积占?；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的?式助溶1. 请依序添加每种溶剂：?10% DMSO ?? 40% PEG300 ?? 5% Tween-80 ?? 45% salineSolubility: ≥ 2.5 mg/mL (5.75 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (5.75 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加? 50 μL Tween-80，混合均匀；然后继续加? 450 μL ?理盐?定容? 1 mL。2. 请依序添加每种溶剂：?10% DMSO ?? 90% (20% SBE-β-CD in saline)Solubility: ≥ 2.5 mg/mL (5.75 mM); Clear solutionPage 1 of 2 www.MedChemExpress.cn

此?案可获得 ≥ 2.5 mg/mL (5.75 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD ?理盐??溶液中，混合均匀。3. 请依序添加每种溶剂：?10% DMSO ?? 90% corn oilSolubility: ≥ 2.5 mg/mL (5.75 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (5.75 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL ??油中，混合均匀。BIOLOGICAL ACTIVITY?物活性Olaparib (AZD2281; KU0059436) 是?种?服有效的 PARP 抑制剂，抑制 PARP-1 和 PARP-2 的 IC50 分别为 5 和 1 nM。Olaparib 是?种?噬 (autophagy) 和有丝分裂 (mitophagy) 激活剂。IC?? & TargetPARP-21 nM (IC50)Mitophagy体外研究Olaparib (AZD2281) is a single digit nanomolar inhibitor of both PARP-1 and PARP-2 that shows standalone activity against BRCA1-deficient breast cancer cell lines. Olaparib is applied to SW620 cell lysates, and identified the IC50 for PARP-1 inhibition to be around 6 nM and the total ablation of PARP-1 activity to be at concentrations of 30?100 nM[1].PARP-15 nM (IC50)tankyrase-11.5 μM (IC50)Autophagy?体内研究Animals bearing SW620 xenografted tumors are treated with Olaparib (10 mg/kg, p.o.) in combination with NSC 362856 (TMZ) (50 mg/kg, p.o.) once daily for 5 consecutive days, after which the tumors are left to grow out[1]. Olaparib increases vascular perfusion in Calu-6 tumors established in a DWC model. Administration of olaparib(50 mg/kg, p.o.) as a single agent (top panel) or in combination with radiation (bottom panel) results in an increase in fluorescence intensity in the Calu-6 tumors[2].PROTOCOLKinase Assay [1]This assay determined the ability of Olaparib to inhibit PARP-1 enzyme activity. PARP-2 activity inhibition is measured by using a variation of the PARP-1 assay in which PARP-2 protein (recombinant) is bound down by a PARP-2 specific antibody in a 96-well white-walled plate. PARP-2 activity is measured following 3H-NAD+ DNA additions. After washing, scintillant is added to measure 3H-incorporated ribosylations. For tankyrase-1, an AlphaScreen assay is developed in which HIS-tagged recombinant TANK-1 protein is incubated with biotinylated NAD+ in a 384-well ProxiPlate assay. Alpha beads are added to bind the HIS and biotin tags to create a proximity signal, whereas the inhibition of TANK-1 activity is directly proportional to the loss of this signal. All experiments are repeated at least three times[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay [1]The PF50 value is the potentiation factor, which is calculated as the ratio of the IC50 of the control growth with alkylating agent methylmethane sulfonate (MMS) divided by the IC50 of the MMS combined with the PARP inhibitor. HeLa B cells are used, and Olaparib is tested at a fixed 200 nM concentration for screening with MMS. For the testing of Olaparib on the SW620 colorectal cell line, the concentrations that are used are 1, 3, 10, 100 and 300 nM. Cell growth is assessed by the use of the sulforhodamine B (SRB) assay[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3

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Animal

Administration [2]

Mice[2]

Mice bearing 220-250 mm3 tumors are randomized into 4 treatment groups (n=5): A; vehicle control (10% DMSO in PBS/10% 2-hydroxy-propyl-β-cyclodextrin daily for 5 days by oral gavage), B; Olaparib (50 mg/kg daily for 5 days by oral gavage), C; 10 Gy fractionated radiotherapy (2 Gy daily for 5 days), D; Olaparib and 10 Gy (5×2 Gy) fractionated radiotherapy (with olaparib given 30 min prior to each daily 2 Gy dose of radiation). Tumor volume measurements are determined daily until they reached 1000 mm3. The number of days for each individual tumor to quadruple in size from the start of the treatment (relative tumor volume×4; RTV4) is calculated for the individual tumors in each group.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

客户使?本产品发表的科研?献

????Nature. 2018 Nov;563(7729):131-136.????Cell. 2019 Jan 24;176(3):505-519.e22.????Cancer Discov. 2018 Mar;8(3):354-369.????Cancer Discov. 2017 Sep;7(9):984-998.????Mol Cell. 2019 Sep 19;75(6):1299-1314.e6.

See more customer validations on www.MedChemExpress.cnREFERENCES

[1].?Menear KA, et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91

[2].?Senra JM, et al. Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft.Mol Cancer Ther. 2011 Oct;10(10):1949-58.

[3].?Yasukawa M, et al. Synergetic Effects of PARP Inhibitor AZD2281 in Oral Squamous Cell Carcinoma in Vitro and in Vivo. Int J Mol Sci. 2016 Feb 24;17(3):272.

[4].?Bian X, et al. PTEN deficiency sensitizes endometrioid endometrial cancer to compound PARP-PI3K inhibition but not PARP inhibition as monotherapy. Oncogene. 2018 Jan 18;37(3):341-351.

McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.

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