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（ 母液浓度为 40 mg/mL ）, 如您需要配置的浓度超过该产品的溶解度，请先与我们客服联系。| 中文名称: | Agerafenib hydrochloride 一键复制产品信息 | ||||
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| 英文名称: | Agerafenib hydrochloride | ||||
| 别名: | Agerafenib hydrochloride CEP-32496hydrochloride;RXDX-105hydrochloride | ||||
| CAS No: | 1227678-26-3 | 分子式: | C24H23ClF3N5O5 | 分子量: | 553.92 |
| CAS No: | 1227678-26-3 | ||||
| 分子式: | C24H23ClF3N5O5 | ||||
| 分子量: | 553.92 | ||||
包装规格：
5mg 25mg in glass bottle
产品描述：
基本信息
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产品编号： |
A12285 |
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产品名称： |
Agerafenib hydrochloride |
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CAS: |
1227678-26-3 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
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分子量 |
553.92 |
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化学名： |
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生物活性
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产品描述 |
一种口服高效的BRAFV600E抑制剂 |
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靶点 |
BRafV600E 14nM(Kd) |
Braf 36nM(Kd) |
CRAF 39nM(Kd) |
c-Kit 2nM(Kd) |
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Ret 2nM(Kd) |
LCK 2nM(Kd) |
Abl-1 3nM(Kd) |
VEGFR- 28nM(Kd) |
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CSF-1R 9nM(Kd) |
EPHA2 14nM(Kd) |
EGFR 22nM(Kd) |
c-Met 513nM(Kd) |
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JAK-2 4700nM(Kd) |
MEK-1 7100nM(Kd) |
MEK-2 8300nM(Kd) |
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体外研究 |
Agerafenib (CEP-32496) exhibits high potency against several BRAFV600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAFV600Eversus those containing wild-type BRAF. Agerafenib (CEP-32496) exhibits potent binding (BRAFV600E Kd=14nM) and cellular activity (pMEK IC50=82nM and A375 proliferation IC50=78nM), with activity in the proliferation assay. CEP-32496 also exhibits a favorable CYP450 inhibition profile, with measured IC50 values greater than 10μM versus the CYP1A2, CYP2C9, CYP2D6, and CYP3A4 isoforms and an IC50=3.4μM versus CYP2C19 |
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体内研究 |
Oral administration of Agerafenib (CEP-32496) to Colo-205 tumor xenograft-bearing mice results in significant inhibition of pMEK in tumor cell lysates. For instance, a single 30 mg/kg (po) dose of Agerafenib (CEP-32496) leads to a 50 and 75% inhibition of normalized pMEK in tumor lysates at the 2 and 6 h postdose time point, respectively (p<0.03), while a 55 mg/kg (po) dose resulted in a 75% to 57% (p<0.03) inhibition of pMEK at 2 through 10 h post administration, with normalization to baseline by 24 h. Agerafenib (CEP-32496) exhibits an exceptional PK profile in mouse, dog, and cynomolgus monkey. Administration of Agerafenib (CEP-32496) to beagle dogs (single dose of 1 mg/kg iv and 10 mg/kg po) results in low clearance (CL=5.0 (mL/min)/kg) and excellent bioavailability (%F=100). Similarly, in cynomolgus monkey, the administration of Agerafenib (CEP-32496) (single dose of 1 mg/kg iv and 10 mg/kg po) leads to high oral exposure due to low clearance (CL=6.7 mL/min/kg) and excellent bioavailability (%F=100) |
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推荐实验方法(仅供参考)
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Cell Assay |
A375 cells are seeded at 10,000 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. The test compounds (e.g., Agerafenib (CEP-32496); 10μM) are then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 h. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50 values are derived using a 9-point curve and are presented as mean values from experiments performed in duplicate |
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Animal Administration |
Mice Six to eight week old athymic nu/nu nude mice (20-25 g) are inoculated subcutaneously with Colo-205 tumor cells (1×106/mouse) in the right flank. Upon reaching an average tumor volume of 150-200 mm3 (10-12 days post implantation), animals are randomized into treatment groups (n=10 mice/group). Each group is dosed orally for 14 days with either vehicle only (22% HPβCD) or with Agerafenib (CEP-32496) at 10, 30, or 100 mg/kg twice daily (BID), and each dose of drug is given in a volume of 0.1 mL per 20 g of body weight, adjusted for the body weight of the animal. Tumor volumes are measured three times weekly using vernier calipers, and volumes are calculated |
保存条件：
-20℃
UN码：
HazardClass：
危害声明：
安全说明：
搜索质检报告(COA)
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
(2).jpg)
体内配方的制备方法: 取 50μLDMSO 母液，添加 300 μLPEG300 混匀澄清，再加 50μLTween80, 混匀澄清，再加 600μLSaline/PBS/ddH2O 混匀澄清
方案所需的各种助溶剂如： DMSO ， PEG300 / PEG400 ， Tween 80 ， SBE-β-CD ， 玉米油 等， 均可点击跳转或在网站搜索购买。
母液，添加 300 μLPEG300 混匀澄清，再加 50μLTween80, 混匀澄清，再加 600μLSaline/PBS/ddH2O 混匀澄清方案所需的各种助溶剂如： DMSO ， PEG300 / PEG400 ， Tween 80 ， SBE-β-CD ， 玉米油 等， 均可点击跳转或在网站搜索购买。
以上为“动物实验计算换算器”的使用方法举例，并不是具体某个试剂的配制，请根据您的实验动物和给药方式选择适当的溶解方案。
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL Saline/PBS/ddH2O，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
剂量转换
对于不同动物的给药剂量换算，您也可以参考 更多
