Doramapimod (BIRB 796)
中文名称：达马莫德
Doramapimod (BIRB 796)是一种泛p38 MAPK抑制剂，在无细胞试验中作用于p38α/β/γ/δ的IC50分别为38 nM，65 nM，200 nM 和520 nM，并且能够与p38α结合，在THP-1细胞中Kd为0.1 nM，比作用于JNK2选择性高330倍，对c-RAF，Fyn 和Lck具有较弱的抑制作用，对ERK-1，SYK，IKK2也有微弱抑制作用。
Doramapimod (BIRB 796) Chemical Structure
CAS: 285983-48-4
产品质控
批次：
纯度：
99.99%
99.99
Doramapimod (BIRB 796)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 |
|---|---|---|---|---|---|
| U937 | Antiinflammatory assay | 2 hrs | Antiinflammatory activity in differentiated human U937 cells assessed as inhibition of LPS-induced TNFalpha production preincubated for 2 hrs followed by LPS-stimulation for 4 hrs by sandwich ELISA relative to vehicle-treated control, IC50 = 0.015 μM. | 26800309 | |
| whole blood cells | Antiinflammatory assay | 4 hrs | Antiinflammatory activity in human whole blood cells assessed as inhibition of LPS-induced TNFalpha production after 4 hrs by time-resolved fluorescence assay, IC50 = 0.6 μM. | 22749282 | |
| KNS-62 | Growth Inhibition Assay | IC50=42.6296 μM | SANGER | ||
| CAL-72 | Growth Inhibition Assay | IC50=42.03 μM | SANGER | ||
| SW756 | Growth Inhibition Assay | IC50=40.9385 μM | SANGER | ||
| MOLT-4 | Growth Inhibition Assay | IC50=38.8391 μM | SANGER | ||
| CTB-1 | Growth Inhibition Assay | IC50=38.4512 μM | SANGER | ||
| LB831-BLC | Growth Inhibition Assay | IC50=37.6541 μM | SANGER | ||
| SK-NEP-1 | Growth Inhibition Assay | IC50=36.6106 μM | SANGER | ||
| HTC-C3 | Growth Inhibition Assay | IC50=36.2355 μM | SANGER | ||
| RT-112 | Growth Inhibition Assay | IC50=35.9879 μM | SANGER | ||
| ChaGo-K-1 | Growth Inhibition Assay | IC50=35.6032 μM | SANGER | ||
| SK-N-AS | Growth Inhibition Assay | IC50=35.0714 μM | SANGER | ||
| SW1116 | Growth Inhibition Assay | IC50=34.4838 μM | SANGER | ||
| EM-2 | Growth Inhibition Assay | IC50=33.5511 μM | SANGER | ||
| NCI-H2009 | Growth Inhibition Assay | IC50=33.4007 μM | SANGER | ||
| AM-38 | Growth Inhibition Assay | IC50=32.9931 μM | SANGER | ||
| HOP-62 | Growth Inhibition Assay | IC50=32.2701 μM | SANGER | ||
| HCC1419 | Growth Inhibition Assay | IC50=32.1119 μM | SANGER | ||
| MHH-ES-1 | Growth Inhibition Assay | IC50=31.941 μM | SANGER | ||
| DBTRG-05MG | Growth Inhibition Assay | IC50=28.5651 μM | SANGER | ||
| U-2-OS | Growth Inhibition Assay | IC50=28.5515 μM | SANGER | ||
| NCI-H1703 | Growth Inhibition Assay | IC50=28.0413 μM | SANGER | ||
| NCI-H2126 | Growth Inhibition Assay | IC50=27.3975 μM | SANGER | ||
| HCC1937 | Growth Inhibition Assay | IC50=27.2238 μM | SANGER | ||
| H-EMC-SS | Growth Inhibition Assay | IC50=26.9245 μM | SANGER | ||
| COLO-741 | Growth Inhibition Assay | IC50=26.3329 μM | SANGER | ||
| KYSE-510 | Growth Inhibition Assay | IC50=26.1612 μM | SANGER | ||
| HOS | Growth Inhibition Assay | IC50=25.9292 μM | SANGER | ||
| HuO-3N1 | Growth Inhibition Assay | IC50=25.8185 μM | SANGER | ||
| HCC1806 | Growth Inhibition Assay | IC50=24.7799 μM | SANGER | ||
| KYSE-270 | Growth Inhibition Assay | IC50=24.5573 μM | SANGER | ||
| EoL-1-cell | Growth Inhibition Assay | IC50=0.34763 μM | SANGER | ||
| DU-145 | Growth Inhibition Assay | IC50=3.93811 μM | SANGER | ||
| GOTO | Growth Inhibition Assay | IC50=6.39161 μM | SANGER | ||
| NCI-H358 | Growth Inhibition Assay | IC50=7.538 μM | SANGER | ||
| IST-MES1 | Growth Inhibition Assay | IC50=7.95637 μM | SANGER | ||
| KP-N-YN | Growth Inhibition Assay | IC50=8.2019 μM | SANGER | ||
| T-24 | Growth Inhibition Assay | IC50=8.40673 μM | SANGER | ||
| MPP-89 | Growth Inhibition Assay | IC50=8.46251 μM | SANGER | ||
| NCI-SNU-1 | Growth Inhibition Assay | IC50=9.06739 μM | SANGER | ||
| BFTC-905 | Growth Inhibition Assay | IC50=10.1233 μM | SANGER | ||
| MS-1 | Growth Inhibition Assay | IC50=10.8235 μM | SANGER | ||
| NBsusSR | Growth Inhibition Assay | IC50=10.8235 μM | SANGER | ||
| BEN | Growth Inhibition Assay | IC50=13.1264 μM | SANGER | ||
| HMV-II | Growth Inhibition Assay | IC50=14.2309 μM | SANGER | ||
| NCI-H1581 | Growth Inhibition Assay | IC50=17.0447 μM | SANGER | ||
| ES8 | Growth Inhibition Assay | IC50=17.167 μM | SANGER | ||
| LC-2-ad | Growth Inhibition Assay | IC50=17.4366 μM | SANGER | ||
| EW-13 | Growth Inhibition Assay | IC50=17.9516 μM | SANGER | ||
| AN3-CA | Growth Inhibition Assay | IC50=18.1 μM | SANGER | ||
| DB | Growth Inhibition Assay | IC50=18.7923 μM | SANGER | ||
| SK-MEL-1 | Growth Inhibition Assay | IC50=20.3683 μM | SANGER | ||
| CAPAN-1 | Growth Inhibition Assay | IC50=22.1884 μM | SANGER | ||
| NCI-H2228 | Growth Inhibition Assay | IC50=23.6668 μM | SANGER | ||
| HOP-92 | Growth Inhibition Assay | IC50=24.3838 μM | SANGER | ||
| KARPAS-299 | Growth Inhibition Assay | IC50=43.3233 μM | SANGER | ||
| HEL | Growth Inhibition Assay | IC50=45.4646 μM | SANGER | ||
| KP-4 | Growth Inhibition Assay | IC50=46.7361 μM | SANGER | ||
| NEC8 | Growth Inhibition Assay | IC50=47.1661 μM | SANGER | ||
| G-402 | Growth Inhibition Assay | IC50=48.7012 μM | SANGER | ||
| Sf21 | Function assay | Binding affinity to wild type human biotin labelled p38 alpha (9 to 352 residues) expressed in sf21 insect cells SPR analysis, Kd = 0.000123 μM. | 28834431 | ||
| THP1 | Function assay | Inhibition of LPS-induced TNFalpha production in human THP1 cells, IC50 = 0.013 μM. | 18325768 | ||
| THP1 | Function assay | Inhibition of LPS-induced TNFalpha production in human THP1 cells, IC50 = 0.018 μM. | 19356929 | ||
| THP1 | Function assay | Inhibition of LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in THP-1 cells, EC50 = 0.018 μM. | 12086485 | ||
| THP | Function assay | Tested for inhibition of Tumor necrosis factor, alpha in THP cells, EC50 = 0.018 μM. | 14561087 | ||
| THP1 | Function assay | Inhibition of LPS-induced TNFalpha production in THP1 cells, IC50 = 0.018 μM. | 17560108 | ||
| THP1 | Function assay | Inhibition of LPS-stimulated TNFalpha production in human THP1 cells, IC50 = 0.018 μM. | 18462940 | ||
| HLF | Function assay | Inhibition of p38alpha phosphorylation in IL-1-alpha-stimulated HLF cells, IC50 = 0.047 μM. | 18602262 | ||
| HLF | Function assay | Inhibition of HSP27 phosphorylation in IL-1-alpha-stimulated HLF cells, IC50 = 0.058 μM. | 18602262 | ||
| HEK293F | Function assay | Inhibition of sodium arsenate activated N-terminal GST-tagged Brugia malayi MPK1 expressed in HEK293F cells using FAM-p38tide as substrate by IMAP assay, IC50 = 0.14 μM. | 29541362 | ||
| BL21(DE3) | Function assay | Inhibition of p38alpha active form expressed in Escherichia coli BL21(DE3) cells by HTRF assay, IC50 = 0.25 μM. | 19928858 | ||
| 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 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Doramapimod (BIRB 796)是一种泛p38 MAPK抑制剂，在无细胞试验中作用于p38α/β/γ/δ的IC50分别为38 nM，65 nM，200 nM 和520 nM，并且能够与p38α结合，在THP-1细胞中Kd为0.1 nM，比作用于JNK2选择性高330倍，对c-RAF，Fyn 和Lck具有较弱的抑制作用，对ERK-1，SYK，IKK2也有微弱抑制作用。 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | BIRB 796是第一个进入三期临床试验的p38 MAPK抑制剂。 | ||||||||||
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | BIRB 796作用于ERK-1,SYK,IKK2β,ZAP-70,EGFR激酶,HER2,蛋白激酶 A(PKA),PKC,PKC-α,PKC-β(I和II)和PKC-γ没有明显抑制效果。BIRB 796通过在吗啉氧和p38α的ATP结合域间形成氢键，显著提高亲和力。BIRB 796是作用于人类p38 MAPK的最有效和分离最慢的抑制剂之一。[1] BIRB 796 有效抑制c-Raf-1和Jnk2α2，IC50分别为1.4和0.1 nM。[2] 高浓度BIRB796也抑制SAPK3/p38γ的活性和激活。BIRB796阻断压力诱导的框架蛋白SAP97磷酸化, SAP97是SAPK3/p38γ的底物。BIRB796作用于HEK293细胞，阻断JNK1/2激活和活性,而作用于Hela细胞，不抑制ERK1/ERK2激活和活性。而且, BIRB796与p38 MAPKs或JNK1/2的结合，降低上游激酶MKK6或MKK4磷酸化，而不增强去磷酸化。 [3] BIRB 796 作用于TNF-α和TGF-β1引起的BMSCs，下调IL-6和VEGF分泌。[4] BIRB-796有吡唑环 ，使亲脂的末端异丁基基团 与低选择性位点结合，甲苯基环与高选择性位点结合。BIRB-796也抑制B-Raf和Abl，IC50分别为83 nM 和14.6 μM。 [5] |
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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 / γ-H2AX mTOR / p-S6K / S6K / p-MK2 / MK2 / p-Hsp27 / Hsp27 p-p38 / p38 |
|
27082306 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | BIRB 796按30 mg/kg剂量作用于LPS刺激的鼠，抑制TNF-α达84%。作用于患胶原诱导的关节炎鼠显示高效性。[1] BIRB 796口服处理给鼠，具有好的药物动力学特征。[2] |
|
|---|---|---|
| 动物实验 | Animal Models | 患胶原诱导的关节炎雌性Balb/c鼠 |
| Dosages | 1 mg/kg(静脉注射)或10 mg/kg(口服) | |
| Administration | 静脉注射或口服 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02211885 | Completed | Healthy |
Boehringer Ingelheim |
October 2002 | Phase 1 |
化学信息&溶解度
| 分子量 | 527.66 | 分子式 | C31H37N5O3 |
| CAS号 | 285983-48-4 | SDF | Download Doramapimod (BIRB 796) SDF |
| Smiles | CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 100 mg/mL ( (189.51 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 100 mg/mL (189.51 mM) Water : Insoluble |
摩尔浓度计算器 |
|
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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