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Doramapimod

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Chemical Structure| 285983-48-4 同义名 : 度马莫德 ;BIRB 796
CAS号 : 285983-48-4
货号 : A103377
分子式 : C31H37N5O3
纯度 : 99%+
分子量 : 527.657
MDL号 : MFCD09752957
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(227.42 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 30 mg/mL(56.86 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

5% DMSO+40%PEG300+5%Tween80 +50%water 5 mg/mL

生物活性
靶点

  • JNK2

  • p38α

    p38α, Kd:0.1 nM

    p38α, IC50:38 nM
描述 The stress-activated protein kinase (SAPK) p38 isoforms are mitogen-activated protein kinase (MAPK) family members. MAPKs act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The well reported isoforms of p38 MAPKs include p38α, p38β and others. Doramapimod, also termed BIRB 796, is a p38 MAPK inhibitor. The IC50s of doramapimod against p38α determined by kinase assay at incubation time of 0 min, 30 min and 90 min were 0.08 μM, 0.07 μM and 0.038 μM, respectively, and the data of doramapimod against p38β were 0.38 μM, 0.215 μM and 0.065 μM, respectively at the same time points[3]. The affinity of doramapimod for p38 MAPK was 0.1 nM, and the inhibitory IC50 of it against TNFα in THP-1 cell culture was 18 nM[4]. In multiple myeloma MM1S and U266 cells, 2h treatment by doramapimod at the concentration of 25 nM was sufficient to inhibit phosphorylation of p38 MAPK[5]. In a mouse model of LPS-stimulated TNF-α synthesis, a 65% inhibition of TNF-α synthesis was observed when doramapimod was dosed orally at 10 mg/kg. In a 5 week model of established collagen-induced arthritis using B10.RIII mice, doramapimod produced a 63% inhibition of arthritis severity when dosed orally at 30 mg/kg qd[6].
作用机制 Doramapimod is a p38 MAPK inhibitor. Doramapimod indirectly competed with the binding of ATP, but prior to binding, the kinase underwent a reorganization of the activation loop exposing a critical binding domain and yielded a structure incompatible with ATP binding[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
AM-38 Growth Inhibition Assay IC50=32.9931 μM SANGRER
AN3-CA Growth Inhibition Assay IC50=18.1 μM SANGRER
BEN Growth Inhibition Assay IC50=13.1264 μM SANGRER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02208856 Healthy Phase 1 Completed - -
NCT02211170 Healthy Phase 1 Completed - -
NCT02209831 Healthy Phase 1 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.90mL

0.38mL

0.19mL

9.48mL

1.90mL

0.95mL

18.95mL

3.79mL

1.90mL
参考文献

[1]280(20):19472-9.

[2]9(4):268-72.

[3]Kuma Y, Sabio G, Bain J, Shpiro N, Márquez R, Cuenda A. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem. 2005 May 20;280(20):19472-9.

[4]Pargellis C, Tong L, Churchill L, Cirillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N, Pav S, Regan J. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat Struct Biol. 2002 Apr;9(4):268-72.