LXH254
目录号 : GC19228
A pan-RAF inhibitor
Cas No.:1800398-38-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[1]SCID beige female tumor-bearing NCI-H358 mice, n=8 per group, are randomized into 3 groups 14 days post tumor cell inoculation with an average tumor volume range of 259.44- 262.47mm3. Animals are administered an oral dose of either vehicle, LXH254 at 30mg/kg or 200mg/kg daily for 14 consecutive days at a dosing volume of 10 mL/kg of animal body weight during course of treatment. Tumor volumes are measured by digital caliper 3 times a week and body weights of all animals are recorded through the course of treatment.Female nude tumor bearing Calu6 mice, n=6 per group are randomized into treatment groups on day 17 following tumor implantation, when the average tumor volume is 180 mm3. Treatments with LXH254 are initiated on Day 17 and continued for 16 days. Dosing volume is 10 mL/kg. Tumor volumes are collected at the time of randomization and twice weekly thereafter for the study duration.Nude female mice tumor bearing NCI-H358, n=8 per group, are randomized into 2 groups with an average tumor volume range of 275.74 mm3. Animals are administered an oral dose of either vehicle or LXH254 at 100 mg/kg daily for 14 consecutive days at a dosing volume of 10 mL/kg of animal body weight during course of treatment. Tumor volumes are measured by digital caliper 3 times a week and body weights of all animals are recorded through the course of treatment[1]. |
References: [1]. CAPONIGRO, Giordano, et al. THERAPEUTIC COMBINATIONS COMPRISING A RAF INHIBITOR AND A ERK INHIBITOR. WO 2018051306 A1 20180322 | |
LXH254 is a potent CRAF inhibitor extracted from patent WO2018051306A1, Compound A. LXH254 also is a potent BRAF inhibitor.
LXH254 (Compound A) is an adenosine triphosphate (ATP)-competitive inhibitor of BRAF (also referred to herein as b-RAF or b-Raf) and CRAF (also referred to herein as c-RAF or c- Raf) protein kinases. Throughout the present disclosure, LXH254 is also referred to as a c-RAF (or CRAF) inhibitor or a C-RAF/c-Raf kinase inhibitor. In cell-based assays, LXH254 has demonstrated anti-proliferative activity in cell lines that contain a variety of mutations that activate MAPK signaling. Moreover, LXH254 is a Type 2 ATP -competitive inhibitor of both B-Raf and C-Raf that keeps the kinase pocket in an inactive conformation, thereby reducing the paradoxical activation seen with many B-Raf inhibitors, and blocking mutant RAS-driven signaling and cell proliferation[1].
Treatment with LXH254 (Compound A) generates tumor regression in several KRAS-mutant models including the NSCLC-derived Calu-6 (KRAS Q61K) and NCI-H358 (KRAS G12C). LXH254 exhibits efficacy in numerous MAPK-driven human cancer cell lines and in xenograft tumors representing model tumors harboring human lesions in KRAS, NRAS and BRAF oncogenes[1].
References:
[1]. CAPONIGRO, Giordano, et al. THERAPEUTIC COMBINATIONS COMPRISING A RAF INHIBITOR AND A ERK INHIBITOR. WO 2018051306 A1 20180322
| Cas No. | 1800398-38-2 | SDF | |
| Canonical SMILES | CC1=CC=C(NC(C2=CC(C(F)(F)F)=NC=C2)=O)C=C1C3=CC(N4CCOCC4)=NC(OCCO)=C3 | ||
| 分子式 | C25H25F3N4O4 | 分子量 | 502.49 |
| 溶解度 | DMSO : ≥ 83.3 mg/mL (165.77 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9901 mL | 9.9504 mL | 19.9009 mL |
| 5 mM | 0.398 mL | 1.9901 mL | 3.9802 mL |
| 10 mM | 0.199 mL | 0.995 mL | 1.9901 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。