LY3009120
别名: DP-4978
LY03009120 (DP-4978)是一种有效的泛Raf抑制剂，在A375细胞中对A-raf，B-Raf，和 C-Raf的IC50分别为44 nM，31-47 nM，和 42 nM。LY03009120 可诱导自噬。Phase 1。
LY3009120 Chemical Structure
CAS: 1454682-72-4
产品质控
批次：
纯度：
99.08%
99.08
LY3009120相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| HCT116 | Function assay | <100 nM | Paradoxical activation of RAS/RAF/MEK signaling pathway in human HCT116 cells expressing wild type BRAF assessed as ERK phosphorylation at <100 nM | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.042μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.039μM. | 25965804 | |
| A375 | Function assay | 72 hrs | Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay, IC50=0.037μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.031μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.02μM. | 25965804 | |
| A375 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay, IC50=0.0092μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.044μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.061μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.091μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.098μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.1μM. | 25965804 | |
| HCT116 | Antiproliferative assay | 67 hrs | Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay, IC50=0.22μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.29μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.31μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.38μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.39μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.45μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.47μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.8μM. | 25965804 | |
| A375 | Function assay | 15 mins | Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.97μM. | 25965804 | |
| MV4-11 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.1μM. | 30529543 | |
| SK-MEL-2 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.2μM. | 30529543 | |
| A375 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.3μM. | 30529543 | |
| SW579 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SW579 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM. | 30529543 | |
| HT-29 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM. | 30529543 | |
| HepG2 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay, IC50=2.6μM. | 30529543 | |
| HCT116 | Function assay | Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA, IC50=0.15μM. | 25965804 | ||
| A375 | Function assay | In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as plasma concentration required to inhibit ERK phosphorylation by 50%, INH=0.165μM. | 25965804 | ||
| A375 | Function assay | Inhibition of desthiobiotin-ATP acylphosphate probe binding to B-Raf in human A375 cells by MS analysis, IC50=0.031μM. | 30529543 | ||
| A375 | Function assay | Inhibition of desthiobiotin-ATP acylphosphate probe binding to C-Raf in human A375 cells by MS analysis, IC50=0.042μM. | 30529543 | ||
| A375 | Function assay | Inhibition of desthiobiotin-ATP acylphosphate probe binding to A-Raf in human A375 cells by MS analysis, IC50=0.044μM. | 30529543 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | LY03009120 (DP-4978)是一种有效的泛Raf抑制剂，在A375细胞中对A-raf，B-Raf，和 C-Raf的IC50分别为44 nM，31-47 nM，和 42 nM。LY03009120 可诱导自噬。Phase 1。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | LY3009120抑制A375和 HCT116细胞的生长，IC50分别为9.2和220 μM。LY3009120抑制酪氨酸激酶KDR，IC50为3.9 μM。[1] | |||
|---|---|---|---|---|
| 激酶实验 | 使用KiNativ试验测定激酶活性 | |||
| 化合物在A375细胞裂解物中使用基于ATP的探针在5 µM下筛选。IC50值以微摩尔单位表示。细胞沉淀重悬浮在4体积裂解缓冲液[25 mM Tris pH 7.6，150 mM NaCl，1% CHAPS，1% Tergitol NP-40 型，1% v/v 磷酸酶抑制剂混合物II]中，使用尖端超声波仪声处理，并均质化。裂解产物通过100,000 g下离心分离30分钟除去。澄清的裂解液通过0.22 μM注射过滤器和凝胶过滤到反应缓冲液[20 mM Hepes pH 7.8，150 mM NaCl，0.1% triton X-100，1% v/v 磷酸酶抑制剂混合物II]。抑制剂处理和探针标记之前，将终浓度为20 mM 的MnCl2加入裂解液。用于IC50测定的终抑制剂浓度为10，1，0.1，和 0.01 μM。ATP竞争性实验在1,000，100，10，和1 μM ATP下进行。所有抑制剂的处理在室温下进行。 | ||||
| 细胞实验 | 细胞系 | A375 和 HCT116 细胞 | ||
| 浓度 | 0.51 μM | |||
| 孵育时间 | 67 h | |||
| 方法 | 简而言之，细胞在DMEM高浓度葡萄糖中生长，用10%胎牛血清和1%青霉素/链霉素/L-谷氨酰胺增补，在37℃，5% CO2，和95%湿度下培育。允许细胞扩增到70-95%的融合度。连续稀释的测试化合物分配加入到384孔黑色透明底板。每孔加入包含625个细胞的50 μL完全生长培养基。板在37℃，5% CO2，和95%湿度下培育67小时。然后，10 μL包含440 μM 刃天青的PBS溶液加入板的每孔中，板在37℃，5% CO2，和95%湿度下再培育5小时。板在Synergy2阅读器上使用540 nm激发波长和600 nm发射波长读取。得到的数据使用Prism软件分析以计算IC 50值。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-EGFR / EGFR / p-BRAF / BRAF / p-CRAF / CRAF / p-MEK / MEK / p-AKT / AKT Beclin-1 / Mcl-1 / LC3 / p62 |
|
27999210 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | 在负荷BRAF V600E ST019VR PDX肿瘤的大鼠体内，LY3009120 (15 or 30 mg/kg, p.o.)剂量依赖性抑制肿瘤生长。在负荷A375异种移植物的裸鼠体内，LY3009120 (3到50 mg/kg, p.o.)单剂量口服治疗剂量依赖性抑制磷酸-ERK，4.36 mg/kg剂量下抑制50%磷酸- ERK (EC50)，68.9 ng/mL或165 nM血浆浓度下达到50%磷酸- ERK (EC50) 抑制率。[1] | |
|---|---|---|
| 动物实验 | Animal Models | 负荷BRAF V600E ST019VR PDX肿瘤的雌性 NIH裸鼠 |
| Dosages | 30 mg/kg | |
| Administration | p.o. | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02014116 | Terminated | Neoplasms|Neoplasm Metastasis|Melanoma|Carcinoma Non-Small-Cell Lung|Colorectal Neoplasms |
Eli Lilly and Company |
November 26 2013 | Phase 1 |
化学信息&溶解度
| 分子量 | 424.51 | 分子式 | C23H29FN6O |
| CAS号 | 1454682-72-4 | SDF | Download LY3009120 SDF |
| Smiles | CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 20 mg/mL ( (47.11 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
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）
mg/kg
g
μL
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Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
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，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
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 ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：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。
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常见问题及建议解决方法
问题 1:
I am trying to figure out solubility of the drug LY3009120 Catalog #7842 for in vivo studies. I need some details on the formulation and how it is made to dissolve the chemical?
回答：
It can dissolve in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O at 1 mg/ml clearly, and in 0.5% CMC Na at 30 mg/ml as a suspension.
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