资料发布时间:2018-10-30 14:50:00 最后更新时间: 2021-06-09 15:17:08
【药品简介】 奥拉帕尼是多聚二磷酸腺苷核糖聚合酶(PARP)抑制剂,用于治疗BRCA基因突变的肿瘤, 比如卵巢癌,乳腺癌,前列腺癌。PARP酶涉及细胞的正常功能,如DNA的转录和 DNA修复。美国药监局临床研究显示:奥拉帕尼无论是作为单药治疗或联合铂类为基础的化疗,均能够抑制试管中肿瘤细胞的生长,和减少人类肿瘤的生长
【适应症状】 奥拉帕尼,1)复发卵巢癌的维持治疗: ①对于上皮性复发性卵巢癌成人患者的维持治疗 ②对铂类敏感或部分敏感的输卵管或原发性腹膜癌的化疗。 2)接受3线或以上化疗方案后仍有进展的gBRCA基因突变的晚期卵巢癌。 3)BRCA基因突变的HER2阴性的转移性乳腺癌:①曾接受新辅助化疗、辅助化疗、转移性化疗的有害或可疑有害的gBRCA基因突变、HER2阴性的转移性乳腺癌患者②激素受体阳性的患者需先进行内分泌治疗,不适合用内分泌治疗的患者再用奥拉帕尼。
【 药品别名 】 奥拉帕尼 Olaparib
印度奥拉帕尼(奥拉帕尼 Olaparib)价格,正品图片,治疗卵巢癌药物, 购买奥拉帕尼请到印度药房官方网站进行购买 【印度药房大全目录】
【 市场参考价格 】 ¥1550.00~2490.00
播放/暂停
生物活性
产品描述 |
Olaparib is a small molecule inhibitor of PARP1/PARP2 (IC50: 5/1 nM) but is less effective against the PARP tankyrase-1 (IC50: 1.5 μM). |
靶点活性 |
PARP1,5 nM (cell free) PARP2,1 nM (cell free) |
实验溶液 |
15% Captisol: 15 mg/mL |
体外活性 |
Following the establishment of a growth-inhibition curve for MMS on SW620 cells, the addition of the PARP-1 inhibitor at nM concentrations dose-dependently increased the effectiveness of MMS. Olaparib (AZD2281) was applied to SW620 cell lysates at a similar concentration range 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]. Concentrations of cisplatin capable of suppressing cell survival by 90% in the presence of 0, 1 or 3 μM AZD2281 were approximately 2.1, 1.5, and 1.2 μM in HSC-2 cells, 1.7, 1.4, and 0.98 μM in Ca9-22 cells, and 2.4, 1.5 and 1.3 μM in SAS cells, respectively. The combination of 1 μM cisplatin and 1 μM AZD2281 attenuated growth rates compared with single treatments of either cisplatin or AZD2281 [2]. The largest difference in drug sensitivity between BRCA2-deficient KB2P cells (IC50: 91 nmol/L) and BRCA2-proficient KP cells (IC50: 8,135 nmol/L) was observed for AZD2281 [3]. |
体内活性 |
Animals bearing SW620 xenografted tumors were treated with AZD2281 (10 mg/kg, po) in combination with TMZ (50 mg/kg, po) once daily for 5 consecutive days, after which the tumors were left to grow out. A considerable inhibition of tumor volumes as compared with that of the TMZ alone group was observed for the TMZ plus AZD2281 combinations [1]. Tumor volumes of control group mice increased during the experimental period. The tumor growth of cisplatin and AZD2281 (25 mg/kg/day, every three days for five treatments) groups significantly decreased compared to the control group, and that of combination group was further decreased [2]. Combination treatment of Calu-6 xenografts with olaparib and fractionated radiotherapy caused significant tumor regression relative to radiotherapy alone. Olaparib alone, when given as single or multiple daily doses, or in combination with fractionated radiotherapy, increased the perfusion of tumor blood vessels [4]. |
激酶实验 |
This assay determined the ability of test compounds to inhibit PARP-1 enzyme activity. The method that was used was as reported. We measured PARP-2 activity inhibition by using a variation of the PARP-1 assay in which PARP-2 protein (recombinant) was bound down by a PARP-2 specific antibody in a 96-well white-walled plate. PARP-2 activity was measured following 3H-NAD+ DNA additions. After washing, scintillant was added to measure 3 H-incorporated ribosylations. For tankyrase-1, an AlphaScreen assay was developed in which HIS-tagged recombinant TANK-1 protein was incubated with biotinylated NAD+ in a 384-well ProxiPlate assay. Alpha beads were added to bind the HIS and biotin tags to create a proximity signal, whereas the inhibition of TANK-1 activity was directly proportional to the loss of this signal. All experiments were repeated at least three times [1]. |
细胞实验 |
HSC-2, Ca9-22, and SAS oral carcinoma cells were seeded in 24-well plates at a density of 2 × 104 cells/well. After overnight incubation, the culture medium was replaced with fresh medium containing various concentrations of PARP inhibitor AZD228 or cisplatin. After 24 h of treatment, the number of viable cells was assessed using an MTT assay as reported previously. Briefly, one-tenth of the fluid volume of 5 mg/mL MTT in RPMI-1640 medium was added to each well, followed by incubation for 4 h at 37 °C. After incubation, the medium was carefully removed and an adequate volume of 0.1 N HCl in isopropanol was added to each well and the resultant formazan crystals was dissolved. Absorbance was determined at 570 nm by microplate reader in 96-well assay plates. All experiments were performed in triplicate [2]. 细胞系: Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D |
动物实验 |
Once the tumor diameter had reached 7 mm, the mice were randomly assigned to the following groups: (a) control (200 μL saline); (b) cisplatin (2 mg/kg per body weight, dissolved in 200 μL sterilized water); (c) AZD2281 (25 mg/kg per body weight, dissolved in 200 μL sterilized water); or (d) combination (both cisplatin and AZD2281). The chemicals were administered intraperitoneally every three days, five times. Although AZD2281 is administered orally in the clinic, intraperitoneal injection was recommended by the manufacturer because of easier manipulation and the ethical constraints associated with oral gavage administration to mice. Tumor size and body weight were measured at the time of administration. The tumor volume was calculated using following equation. Tumor volume = verticality × width × height × 0.5236 Three days after the last administration, all surviving mice were sacrificed [2]. 动物模型:Brca1-/-;p53-/- mammary tumors are generated in K14cre;Brca1F/F;p53F/F mice. |
化学信息
分子量 |
434.46 |
分子式 |
C24H23FN4O3 |
CAS |
763113-22-0 |
溶解度 |
DMSO: 80 mg/mL (184.1 mM) Ethanol: <1 mg/mL Water: <1 mg/mL ( < 1 mg/ml refers to the product slightly soluble or insoluble ) |
储存条件 |
store at -80°C |
备注 |
For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
配制溶液
1 mg | 5 mg | 10 mg | |
1 mM | 2.302 ml | 11.509 ml | 23.017 ml |
5 mM | 0.46 ml | 2.302 ml | 4.603 ml |
10 mM | 0.23 ml | 1.151 ml | 2.302 ml |
50 mM | 0.046 ml | 0.23 ml | 0.46 ml |
奥拉帕尼用于治疗既往接受过三线以上化疗的BRCA突变晚期卵巢癌和铂类药物治疗产生应答后疾病复发的成人卵巢上皮癌、输卵管癌......
每个乳腺癌患者都应该知道病因,有些人是由不良的生活习惯引起的,这种疾病会直接危及患者的生命。因此,发生后应予以重视,然后......
据世界卫生组织调查,41%的中国育龄妇女患有不同程度的妇科疾病,已婚妇女患病率高达70%。 此外,每年有20万至30万中......
近年来,卵巢癌对女性的负面影响越来越大,因此,对卵巢癌的预防和检测意识有待加强。如果患者意外患上卵巢癌,不要失去抗击卵巢......
卵巢癌是女性常见肿瘤之一,是具有很高死亡率的恶性肿瘤。卵巢癌的高发阶段是四十到七十岁,其中以五十岁前后的中年妇女最多。卵......
药物保存的温度建议在室温20-25摄氏度保存,避免儿童直接接触...
卵巢癌的发生与初潮的年龄、绝经的年龄、遗传因素、饮食因素、环境因素等...
卵巢癌的预防首先需要进行定期检查,以便进行早期处理...
卵巢位于盆腔,体积很小,所以卵巢上长个小东西也很难早期发现...
Pharmacy Catalogue
【代购】【有实体店】【在线客服懂中文】
代购+直邮,印度抗癌药跨境医药电商直邮服务,让肿瘤患者能够有更好的选择,平台提供印度就医,印度易瑞沙,吉三代,吉二代,索......
【禁止中国访问 】【印度连锁】【品牌实力】
MedPlus是印度第二大药房连锁店。它经营1555家商店,其中1317家为公司所有,159家为特许经营公司,43家为医......
【药品种类丰富 】【渠道正规】【价格较高】
Wellness Forever是一家生活方式零售药房连锁店,致力于为印度本土客户提供全面的健康服务。目前总收入约为62......
【visa/万事达】 【全球可邮 】【纯线上销售】【可开处方】
Netmeds.com致力于开发印度本土市场,已成为印度领先的在线药店。Netmeds.com通过其全天候在线门户和移动......