LGX818
(Synonyms: 康奈非尼,LGX818) 目录号 : GC16576
An inhibitor of mutant B-Raf kinase
Cas No.:1269440-17-6
Sample solution is provided at 25 µL, 10mM.
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LGX818 is a potent and selective inhibitor of RAF kinase with EC50 value of 3nM in A375 cells [1].
The V600E mutation of B-Raf in the kinase domain results in constitutive activation of B-Raf and promotes cancer development. LGX818 is a RAF kinase inhibitor targeting V600E mutant B-Raf. It has little effect against wild-type BRAF. LGX818 has selective anti-proliferative and apoptotic activity ion in cells expressing BRAFV600E. It shows no significant activity against a panel of 100 kinases and no suppression of cell growth with more than 400 cell lines expressing BRAFV600E. In the A375 human melanoma cell line, LGX818 inhibits the phospho-ERK with EC50 value of 3nM and causes subsequent cell proliferation inhibition with EC50 value of 4nM. In human melanoma xenograft models, oral administration of LGX818 shows strong decrease in phospho-MEK and induces tumor regression [1, 2].
References:
[1] Stuart D D, Li N, Poon D J, et al. Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor. Cancer Research, 2012, 72(8 Supplement): 3790.
[2] Huang T, Karsy M, Zhuge J, et al. B-Raf and the inhibitors: from bench to bedside. J Hematol Oncol, 2013, 6(1): 30.
| Cell experiment [1]: | |
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Cell lines |
Human melanoma A375 (BRAFV600E) cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
3 ~ 900 nM |
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Applications |
In human melanoma A375 (BRAFV600E) cells, LGX818 suppressed phospho-ERK (EC50 = 3 nM), thus potently inhibiting cell proliferation (EC50 = 4 nM). Meanwhile, LGX818 did not show any significant inhibition against a panel of 100 kinases (IC50 > 900 nM) as well as proliferation of > 400 cell lines expressing wild-type BRAF. In addition, biochemical assays showed that the dissociation half-life of LGX818 was >24 hrs. Thus, the inhibition effect of LGX818 remained following drug wash-out. |
| Animal experiment [1]: | |
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Animal models |
BRAF mutant or wild-type human tumor xenograft models |
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Dosage form |
1 ~ 300 mg/kg; p.o. |
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Applications |
At an oral dose as low as 6 mg/kg, LGX818 potently (75%) and continuously (> 24 hrs) decreased phospho-MEK in human melanoma xenograft models (BRAFV600E). In nude mice and rats bearing multiple BRAF mutant human tumors, LGX818 induced tumor regression at the dose as low as 1 mg/kg. Moreover, for BRAF wild-type tumors, LGX818 did not show any activity at the dose up to 300 mg/kg (b.i.d.), with good tolerability and linear increase in exposure. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Stuart D D, Li N, Poon D J, et al. Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor. Cancer Research, 2012, 72(8 Supplement): 3790. | |
| Cas No. | 1269440-17-6 | SDF | |
| 别名 | 康奈非尼,LGX818 | ||
| 化学名 | methyl N-[(2S)-1-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate | ||
| Canonical SMILES | CC(C)N1C=C(C(=N1)C2=CC(=CC(=C2F)NS(=O)(=O)C)Cl)C3=NC(=NC=C3)NCC(C)NC(=O)OC | ||
| 分子式 | C22H27ClFN7O4S | 分子量 | 540.01 |
| 溶解度 | DMF: 25 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 20 mg/ml,Ethanol: 15 mg/ml | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8518 mL | 9.2591 mL | 18.5182 mL |
| 5 mM | 0.3704 mL | 1.8518 mL | 3.7036 mL |
| 10 mM | 0.1852 mL | 0.9259 mL | 1.8518 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet