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】 瑞戈菲尼可广泛抑制与血管生成和肿瘤发生相关的激酶
【适应症状】 瑞格非尼,处方药。肝细胞肝癌:用于前期使用过索拉菲尼的肝细胞肝癌。转移性结直肠癌:用于治疗既往曾用含氟嘧啶、奥沙利铂、伊立替康方案的化疗或抗VEGF药物或抗EGFR药物(如果患者是RAS野生型)的转移性结直肠癌。胃肠道间质性肿瘤:用于治疗既往曾用伊马替尼和舒尼替尼药物的,局部进展的、无法切除的或转移性胃肠道间质性肿瘤(GIST)
【 药品别名 】 拜万戈 瑞戈非尼 Stivarga regorafenib
印度瑞格非尼(拜万戈 瑞戈非尼 Stivarga regorafenib)价格,正品图片,治疗结直肠癌药物, 购买瑞格非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 】 ¥980.00~3030.00
播放/暂停
生物活性
产品描述 |
Regorafenib (BAY 73-4506) is a multi-targeted receptor tyrosine kinase inhibitor (IC50s: 1.5/2.5/4.2/7/13/22 nM for RET/C-RAF/VEGFR2/c-Kit/VEGFR1/PDGFRβ). |
靶点活性 |
Kit,7 nM (cell free) Raf-1,2.5 nM (cell free) RET,1.5 nM (cell free) VEGFR1,13 nM (cell free) VEGFR2,4.2 nM (cell free) B-Raf (V600E),19 nM (cell free) |
实验溶液 |
30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL |
体外活性 |
Regorafenib potently inhibited a distinct set of kinases, including the angiogenic and stromal RTKs VEGFR1-3, TIE2, FGFR1 and PDGFR-b (IC50s: 4-311 nM), and the oncogenic RTKs KIT and RET, along with the intracellular signaling kinases c-RAF/RAF-1 and BRAF and its V600E mutant (IC50s: 1.5-28 nM). Regorafenib potently inhibited VEGFR2 autophosphorylation in NIH-3T3/VEGFR2 cells (IC50: 3 nM). In HAoSMCs, regorafenib inhibited PDGFR-b autophosphorylation after stimulation with PDGF-BB (IC50: 90 nM) [1]. Regorafenib caused a concentration-dependent decrease in Hep3B cell growth (IC50: 5 μM). PLC/PRF/5 cells were similar in their responses to Hep3B cells, but HepG2 cells were more sensitive (IC50: 1 μM) [2]. |
体内活性 |
Treating tumor-bearing rats with a single oral dose of regorafenib at 10 mg/kg caused a significant decrease in tumor perfusion and extravasation of the contrast agent. A significant reduction of the normalized IAUC360 was observed by 10 hr after regorafenib treatment and persisted for up to 2 days when compared with vehicle. Regorafenib dosed qd orally inhibited tumor growth in a dose-dependent manner in multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors. Regorafenib (10–100 mg/kg) effectively inhibited the growth of the Colo-205 xenografts, reaching a TGI of ~75% at day 14 at the 10 mg/kg dose [1]. In murine xenograft models, oral regorafenib, M-2, and M-5 significantly inhibited tumor growth versus controls. Total peak plasma drug concentrations and exposure to M-2 and M-5 in mice after repeated oral dosing with regorafenib 10 mg/kg/day were comparable to those in humans [3]. |
激酶实验 |
In vitro assays using recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFR-b (aa561–aa1106), RAF-1 (aa305–aa648) and BRAFV600E (aa409–aa765) kinase domains were performed as previously described. Initial in vitro kinase inhibition profiling was performed at a fixed 1 μM compound concentration under Millipore standard conditions [10 μM adenosine-50’- triphosphate (ATP) concentration]. Inhibitory concentration of 50% (IC50) values were determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition was measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate. |
细胞实验 |
Each cell line was seeded at 0.3×10^5 cells/2ml of DMEM containing 10% FBS in 35 mm tissue culture dishes. The cells were incubated for 24 h to allow attachment, and then the medium was replaced by fresh culture medium containing Regorafenib at increasing concentrations (1 μM, 2.5 μM, 5 μM, 7.5 μM and 10 μM). In these experimental conditions, the cells were allowed to grow for 72 or 96 h. Time-course experiments on Hep3B cells were performed with 7.5 μM of Regorafenib at short (15, 60, 180 min.), middle (24, 48, 72 and 96 h) or long times (up to seven days). When the cells were treated for long times the drug was replaced with a fresh one. Each experiment included a control with the equivalent concentration of DMSO (solvent control) as the one used for adding Regorafenib. Each experiment was performed in triplicate and repeated 3 times. Subsequent analyses were performed at specific Regorafenib concentrations and incubation times [2]. 细胞系: GIST 882 and TT cells |
动物实验 |
Female athymic NCr nu/nu mice, kept in accordance with Federal guidelines, were subcutaneously inoculated with 5×10^6 Colo-205 or MDAMB-231 cells or implanted with 1 mm^3 786-O tumor fragments. When tumors reached a volume of ~100 mm^3, regorafenib or vehicle control was administered orally qd×21 in the 786-O model, and qd×9 in the Colo-205 and MDA-MB231 models, respectively, at doses of 100, 30, 10, and 3 mg/kg. Paclitaxel was administered intravenously at 10 mg/kg in ethanol/Cremophor ELV/saline (12.5%/12.5%/75%) every 2 days×5. Tumor size (volume) was estimated twice weekly (l×w^2)/2, and the percentage of tumor growth inhibition (TGI) was obtained from terminal tumor weights (1-T/C100). Mice were weighed every other day starting from the first day of treatment. The general health status of the mice was monitored daily [1]. 动物模型:Feathymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O |
化学信息
分子量 |
482.82 |
分子式 |
C21H15ClF4N4O3 |
CAS |
755037-03-7 |
溶解度 |
DMSO: 90 mg/mL (186.4 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 | 2.071 ml | 10.356 ml | 20.712 ml |
5 mM | 0.414 ml | 2.071 ml | 4.142 ml |
10 mM | 0.207 ml | 1.036 ml | 2.071 ml |
50 mM | 0.041 ml | 0.207 ml | 0.414 ml |
瑞戈非尼是第一个结束了索拉非尼唯一肝癌靶向药的新药物,能够 用作二线肝癌的治疗,由拜耳研发生产。 瑞戈非尼的原研药和拜耳......
各项医学研究早已经检验了瑞戈非尼的安全。CORRECT医学研究中瑞戈非尼组270例、安慰剂组35例出现3-4级医治有关不......
结直肠癌是世界上第三大最常见的癌症,每年新增136万例。5年生存期在28%65%之间。过去,转移性直肠癌的主要医治手段以......
瑞戈非尼现阶段主要是使用于胃肠间质瘤和转移性结肠癌的靶向药物治疗。较于安慰剂组,可让受到标准医治后肿瘤处于进展情况期的转......
瑞戈非尼实际上是一个较为新型的抗肿瘤药物,具体的成分便是瑞戈非尼,是一个淡粉色椭圆形薄膜衣片,为口服多激酶抑制剂。 瑞戈......
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......