AZD2281 (Olaparib) 奥拉帕尼

生物活性

Olaparib (AZD2281, Ku-0059436)是一种选择性的PARP1/2抑制剂，IC50为5 nM/1 nM，比对Tankyrase-1的作用强300倍。Olaparib是PARP抑制剂，也作用于BRCA1或BRCA2突变。Olaparib对端锚(聚合)酶-1作用效果不大，IC50值大于。Olaparib浓度为30-100 nM作用于SW620细胞，使PARP-1失活。

实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）

细胞实验
细胞系	SW620 colorectal cell line
方法	Potentiation of MMS Cytotoxicity by 47 Determined by the Use of Sulforhodamine B Cell Growth Assays. SW620 cells were seeded in 96-well plates and were left to attach overnight. Cells were preincubated with vehicle control (DMSO) or with a single concentration of KU-0059436 (1, 3, 10, 30, 100 or 300 nM) for 1 h before the addition of increasing concentrations of MMS. Cells were incubated in the presence of each drug combination for 4 days before cell growth was quantified by the use of an SRB assay.44 Data were calculated from triplicate wells as the mean percentage of cell growth relative to KU-0059436-only wells, and (SE and IC50 were calculated by the use of XL-FIT 4 software. SW620 cells showed <24% growth inhibition (>76% cell growth) when only KU-0059436 was used at concentrations below 300 nM (data not shown).
浓度	1, 3, 10, 100 and 300 nM
处理时间	4 days

动物实验
动物模型	mouse bearing SW620 xenografted tumors
配制	methylcellulose/PBS
剂量	10 mg/kg once daily for 5 consecutive days
给药处理	orally

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.3017 mL	11.5085 mL	23.0171 mL
5 mM	0.4603 mL	2.3017 mL	4.6034 mL
10 mM	0.2302 mL	1.1509 mL	2.3017 mL

使用AbMole产品发表的文献

• 

  Cell. 2019 Jun 13;177(7):1903-1914.e14.

  Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.
  AZD2281 (Olaparib)购买自AbMole

• 

  Clin Cancer Res. 2019 Mar 1;25(5):1664-1675.

  The Ewing Family of Tumors Relies on BCL-2 and BCL-XL to Escape PARP Inhibitor Toxicity.
  AZD2281 (Olaparib)购买自AbMole

• 

  Int J Biol Sci. 2018 Oct 3;14(13):1769-1781.

  Inhibition of AKT suppresses the initiation and progression of BRCA1-associated mammary tumors.
  AZD2281 (Olaparib)购买自AbMole

客户产品验证及相关生物数据

	数据来源	Int J Biol Sci (2018 Oct). Figure 5. Olaparib (Abmole Bioscience, Houston, USA)
	方法	IP
	细胞系	mice
	浓度	100 mg/kg
	处理时间	-
	实验结果	The overall RTVs (treated vs. non-treated tumors) for mice bearing Brca1-mutant tumor allografts were 60.8% and 62.6% for mice treated with MK-2206 and olaparib, respectively.

	数据来源	Int J Biol Sci (2018 Oct). Figure 4. Olaparib (Abmole Bioscience, Houston, USA)
	方法	IP
	细胞系	mice
	浓度	100 mg/kg
	处理时间	-
	实验结果	In mice co-treated with olaparib and MK-2206, tumor volume was only increased ~1.8-fold at this same time, indicating that these agents exerted a additive effect on tumor growth.

	数据来源	Int J Oncol (2015). Figure 4. AZD2281
	方法	apoptosis assay
	细胞系	HCC‑1428 cells
	浓度	2 μM
	处理时间	4 day
	实验结果	Inhibition of autophagy by knocking down ATG5 also partially inhibited AZD2281-induced apoptosis, suggesting that autophagy contributes to AZD2281-induced cell death in BRCA mutated breast cancer cells.

	数据来源	Int J Oncol (2015). Figure 1. AZD2281
	方法	Transmission electron microscopy
	细胞系	BRCA1 or BRCA2 mutant breast cancer cell lines
	浓度	2 μM
	处理时间	4 day
	实验结果	The growth inhibition effect of AZD2281 was significantly higher in the BRCA wild-type cell lines with BRCA1 allelic loss than in the BRCA wild-type cell line without BRCA1 allelic loss.

参考文献

Synthetic lethality of PARP and NAMPT inhibition in triple-negative breast cancer cells.
Bajrami et al. EMBO Mol Med. 2012 Aug 30. PMID: 22933245.

Clinical trials and future potential of targeted therapy for ovarian cancer.
Itamochi et al. Int J Clin Oncol. 2012 Aug 28. PMID: 22926640.

PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA proficient triple negative breast cancer to PARP inhibition.
Ibrahim et al. Cancer Discov. 2012 Aug 24. PMID: 22915752.

Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib.
Daemen et al. Breast Cancer Res Treat. 2012 Sep;135(2):505-17. PMID: 22875744.

Olaparib , PARP1 inhibitor in ovarian cancer.
Marchetti et al. Expert Opin Investig Drugs. 2012 Jul 13. PMID: 22788971.