Ralimetinib (LY2228820) dimesylate
Ralimetinib (LY2228820) dimesylate 是一种新型有效的p38 MAPK抑制剂，无细胞试验中IC50为7 nM，不改变p38 MAPK的活化。Phase 1/2。
Ralimetinib (LY2228820) dimesylate Chemical Structure
CAS: 862507-23-1
产品质控
批次：
纯度：
99.63%
99.63
Ralimetinib (LY2228820) dimesylate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 |
|---|---|---|---|---|---|
| U-87-MG | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| CD14+ | Function assay | ~800 nM | inhibits osteoclastogenesis from CD14 positive cells | 18397345 | |
| INA-6 | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| RPMI-LR5 | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| RPMI-Dox40 | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| MM.1S | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| U266 | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| RPMI-8226 | Cytoxicity assay | ~1000 nM | no significant cytotoxicity | 18397345 | |
| INA-6 | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| RPMI-LR5 | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| RPMI-Dox40 | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| MM.1S | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| U266 | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| RPMI-8226 | Kinase assay | ~800 nM | inhibits phosphorylation of HSP27 | 18397345 | |
| MDA-MB-231 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| A-2780 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| SK-OV-3 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| LXFA-629 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| NCI-H1650 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| PC-3 | Function assay | 1 μM | reduces tumor-driven cord formation | 23335506 | |
| RAW264.7 | Function assay | ~20 μM | inhibits Anisomycin-stimulated MK2 phosphorylation with IC50 of 35.3 nM | 24356814 | |
| mouse peritoneal macrophages | Function assay | ~20 μM | LPS/IFN-γ–stimulated TNF-α production with IC50 of 6.3 nM | 24356814 | |
| A549 | Function assay | ~20 μM | inhibits LPS-induced CXCL8 production with IC50 of 144.9 nM | 24356814 | |
| MDA-231 | Function assay | ~10 μM | suppresses DKK-1 expression | 26407843 | |
| MCF-7 | Function assay | ~10 μM | suppresses DKK-1 expression | 26407843 | |
| MDA-435 | Function assay | ~10 μM | suppresses DKK-1 expression | 26407843 | |
| PC3 | Function assay | ~10 μM | suppresses DKK-1 expression | 26913608 | |
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Ralimetinib (LY2228820) dimesylate 是一种新型有效的p38 MAPK抑制剂，无细胞试验中IC50为7 nM，不改变p38 MAPK的活化。Phase 1/2。 | ||
|---|---|---|---|
| 特性 | LY2228820是新型有效的p38有丝分裂原活化蛋白激酶(MAPK)通路抑制剂。 | ||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | LY2228820作用于RAW 264.7细胞，抑制p38α,和磷酸MAPKAPK-2(pMK2)水平,IC50分别为7 nM 和 34.3 nM。而且, LY2228820作用于小鼠腹腔巨噬细胞，抑制脂多糖 (LPS)-诱导的TNFα形成, IC50为5.2 nM。[1] 200 nM-800 nM LY2228820作用于多发性骨髓瘤(MM)细胞, 包括INA6, RPMI-8226, U266, 和RPMI-Dox40,通过抑制HSP27磷酸化而显著抑制p38MAPK信号, HSP27是p38MAPK下游靶点,不影响 HSP27表达水平。200 nM-400 nM LY2228820增强细胞毒性和凋亡, 但是LY2228820 单独处理不会抑制MM.1S细胞生长。200 nM-800 nM LY2228820作用于长期骨髓基质干细胞(LT-BMSCs)，骨髓单个核细胞(BMMNCs)，外周血（PB）CD138+，CD138-或外周血（PB）CD14+细胞，也抑制IL-6和MIP-1α分泌。400 nM-800 nM LY2228820也抑制CD14+ 细胞形成破骨细胞。[2] |
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|---|---|---|---|---|
| 激酶实验 | 抑制p38α实验 | |||
| 使用重组人p38α 在标准过滤器中使用ATP[γ-33P] 和EGFR 21肽底物测定抑制p38α的效果。在LY2228820存在时，使用LPS刺激，在小鼠腹腔巨噬细胞测定抑制TNFα效果。在使用LY2228820处理，然后用Anisomycin刺激的RAW 264.7细胞中测定p38α活性。使用磷酸MAPKAPK-2(pMK2)(Thr 334)抗体测定p38α活性水平。 | ||||
| 细胞实验 | 细胞系 | MM细胞,包括 INA6, RPMI-8226, U266,和RPMI-Dox40 | ||
| 浓度 | 200 nM-800 nM | |||
| 孵育时间 | 48小时 | |||
| 方法 | 进行MTT实验和APO 2.7 染色分别测定细胞增殖和凋亡诱导。测定活细胞百分数作为可活力。通过APO 2.7染色测定凋亡。为了测定凋亡细胞中线粒体膜蛋白7A6的表达，用APO 2.7试剂处理细胞20分钟。使用EPICS XL流式细胞仪测定APO 2.7的表达。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-p38 / p38α / p38β / p-MK2 / MK2 / p-HSP27 / HSP27 p-S6K |
|
23335506 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | LY2228820 作用于LPS诱导的小鼠，有效抑制TNFα 形成，半数有效剂量最小阈值 (TMED 50)小于1 mg/kg。LY2228820 作用于患胶原性关节炎(CIA)大鼠模型,有效作用于足肿胀, 骨质糜烂, 和软骨破坏, 半数有效剂量最小阈值(TMED50)为 1.5 mg/kg。[1] |
|
|---|---|---|
| 动物实验 | Animal Models | 脂多糖(LPS)-诱导的Balb/c小鼠 |
| Dosages | 0-20 mg/kg | |
| Administration | 口服处理，每天两次，持续14天 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02860780 | Completed | Advanced Cancer|Metastatic Cancer|Colorectal Cancer|Non-small Cell Lung Cancer |
Eli Lilly and Company |
August 10 2016 | Phase 1 |
| NCT02364206 | Completed | Adult Glioblastoma |
Centre Jean Perrin|National Cancer Institute France|ARC Foundation for Cancer Research |
June 8 2015 | Phase 1|Phase 2 |
| NCT02322853 | Terminated | Postmenopausal|Metastatic Breast Cancer |
Centre Francois Baclesse|National Cancer Institute France|ARC Foundation for Cancer Research |
January 2015 | Phase 2 |
| NCT01393990 | Completed | Advanced Cancer |
Eli Lilly and Company |
September 4 2008 | Phase 1 |
化学信息&溶解度
| 分子量 | 612.74 | 分子式 | C24H29FN6.2CH4O3S |
| CAS号 | 862507-23-1 | SDF | Download Ralimetinib (LY2228820) dimesylate SDF |
| Smiles | CC(C)(C)CN1C2=C(C=CC(=N2)C3=C(N=C(N3)C(C)(C)C)C4=CC=C(C=C4)F)N=C1N.CS(=O)(=O)O.CS(=O)(=O)O | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 100 mg/mL ( (163.2 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : 100 mg/mL (163.2 mM) Ethanol : 7 mg/mL (11.42 mM) |
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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