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中文名称: Agerafenib hydrochloride
英文名称: Agerafenib hydrochloride
CAS No: 1227678-26-3
分子式: C24H23ClF3N5O5
分子量: 553.92
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A12285 Agerafenib hydrochloride ≥98% (psaitong)
包装规格：
5mg 25mg in glass bottle
产品描述：

基本信息

产品编号：

A12285

产品名称：

Agerafenib hydrochloride

CAS:

1227678-26-3

 

储存条件

粉末

-20℃

四年

 

 

分子式：

C24H23ClF3N5O5

溶于液体

 

 

分子量

553.92

 

 

化学名： 

1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride

 

生物活性

产品描述

一种口服高效的BRAFV600E抑制剂

靶点

BRafV600E

14nM(Kd)

Braf

36nM(Kd)

CRAF

39nM(Kd)

c-Kit

2nM(Kd)

Ret

2nM(Kd)

LCK

2nM(Kd)

Abl-1

3nM(Kd)

VEGFR-

28nM(Kd)

CSF-1R

9nM(Kd)

EPHA2

14nM(Kd)

EGFR

22nM(Kd)

c-Met

513nM(Kd)

JAK-2

4700nM(Kd)

MEK-1

7100nM(Kd)

MEK-2

8300nM(Kd)

 

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

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)

 

推荐实验方法(仅供参考)

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

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：
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参考文献 & 客户发表文献

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

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    *选择对应的单位 *空出希望得到的变量，填写另外两个变量

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 )

  • * = *

连续稀释计算器方程

  • 连续稀释

  • 初始浓度:
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  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
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