基本信息

产品描述

Olaparib (AZD2281, KU0059436)是选择性的PARP1/2抑制剂，IC50为5 nM/1 nM，其对PARP1/2的作用比对Tankyrase-1效果高300倍。

靶点（IC50 & Targe）

PARP1,5 nM (cell free)

PARP2,1 nM (cell free)

体外研究

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。与BRCA1和BRCA2充足细胞系(Hs578T,MDA-MB-231,T47D)相比，BRCA1缺陷细胞系(MDA-MB-463和HCC1937)对Olaparib过分敏感[1] Olaparib抑制PARP，阻断碱基切除修复，导致KB2P细胞对Olaparib强烈敏感。结果导致在DNA复制时由单链断裂转变为双链断裂，由此激活BRCA2依赖的重组途径。[2]

体内研究

Olaparib有效作用于Brca1-/-;p53-/- 乳腺肿瘤 (每天按50 mg/kg剂量腹腔注射),但是对 HR缺陷的Ecad-/-;p53-/-乳腺肿瘤没有效果。Olaparib作用于携带肿瘤的鼠没有剂量限制毒性。[3] Olaparib已经用于治疗BRCA突变的肿瘤, 比如卵巢癌，胸腺癌，前列腺癌。此外，Olaparib抑制ATM缺陷的肿瘤细胞具有选择性，说明Olaparib可作为治疗ATM突变的淋巴肿瘤的潜在试剂。[4]

激酶实验

体外独立酶实验:

通过PARP-1实验测定PARP-2抑制活性，实验在96孔板上进行，PARP-2特定抗体与重组PARP-2蛋白结合。加入3H-NAD+DNA测定PARP-2活性。 冲洗后，加入闪烁剂测定3H-渗透的核糖基化。通过AlphaScreen实验测定端锚聚合酶-1, 实验中HIS标签重组TANK-1蛋白和生物素化的NAD+ 在384孔Proxi板上温育。 加入Alpha 磁珠，与HIS和生物素化的标签结合，产生邻近信号，测定信号消失的比例来计算TANK-1抑制活性。

细胞实验

Cell lines: 胸腺癌细胞系SW620结肠, A2780卵巢,HCC1937,Hs578T,MDA-MB-231,MDA-MB-436,和T47D

Concentrations: 1到300 nM

Incubation Time: 7-14天

Method:通过成株实验测定Olaparib毒性。Olaparib溶于DMSO中，用培养基稀释。细胞接种在六孔板上，过夜使粘附。然后加入不同浓度Olaparib，温育7-14天。计算存活菌落，测定IC50值。

(Only for Reference)

动物实验

Animal Models: 携带Brca1-/-;p53-/-乳腺癌的 K14cre;Brca1F/F;p53F/F鼠

Formulation: 50 mg/mL储存在含10% 2-羟丙基-β-环糊精/PBS的DMSO中

Dosages: 50 mg/kg

Administration: 按10 μL/g剂量腹腔注射

(Only for Reference)

参考文献

[1] Menear KA, et al. J Med Chem, 2008, 51(20), 6581-6591.

[2] Evers B, et al, Clin Cancer Res, 2008, 14(12), 3916-3925.

[3] Rottenberg S, et al, Proc Natl Acad Sci U S A, 2008, 105(44), 17079-17084.

[4] Weston VJ, et al, Blood, 2010, 116(22), 4578-4587.

安全信息

图形或危害标志
提示语	Danger
危险说明	H301 H360 H372 H315 H319 H335
防范说明	P260 P281 P301+P310 P330 P314
UN号码	2811
危险分类	6.1
包装等级	III

基本信息

Ref#
46629

分子式
C24H23FN4O3

分子量
610.67

GHS危害和防范说明

Hazard Statements
H301 H360D H372

Precautionary Statements
P264 P301+P330+P331 P201 P280 P308+P313

安全信息

危险等级
6.1

基本信息

安全信息

图形或危害标志
危险性说明	H302: Harmful if swallowed. H315: Causes skin irritation. H319: Causes serious eye irritation. H335: May cause respiratory irritation. H372: Causes damage to organs (blood). H360D: May damage the unborn child.
防范说明	P201: Obtain special instructions before use. P202: Do not handle until all safety precautions have been read and understood. P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing P264: Wash hands thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P281: Use personal protective equipment as required. P301 + P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: . P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P314: Get medical advice/attention if you feel unwell. P321: Specific treatment (see . on this label). P330: Rinse mouth. P332 + P313: If skin irritation occurs: Get medical advice/ attention. P337 + P313: If eye irritation persists: Get medical advice/attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P362: Take off contaminated clothing and wash before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to local regulations.