公告提醒:爱必信所有产品和服务仅用于科学研究,不用于临床应用及其他用途提供产品和服务(也不为任何个人提供产品和服务)!

抑制剂描述:

产品名称:BIRB 796 (Doramapimod)

产品别名:见爱必信官网

英文别名:BIRB 796 (Doramapimod)

靶点:p38 MAPK

CAS:285983-48-4

纯度:>98%

外观:见爱必信官网

保存方法:Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.

描述:

BIRB 796 (Doramapimod)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。

溶解性:DMSO : 52.8 mg/mL (100 mM)
Ethanol : 26.4 mg/mL (50 mM)

体外研究:

BIRB 796 shows no significant inhibition to ERK-1, SYK, IKK2β, ZAP-70, EGF receptor kinase, HER2, protein kinase A (PKA), PKC, PKC-α, PKC-β (I and II) and PKC-γ. BIRB 796 greatly improves binding affinity by forming a hydrogen bond between the morpholine oxygen and the ATP-binding domain of p38α. BIRB 796 represents one of the most potent and slowest dissociating inhibitors against human p38 MAP kinase now known. BIRB 796 potently inhibits c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. BIRB796 also inhibits the activity and the activation of SAPK3/p38γ at a higher concentration than it does in p38α. BIRB796 blocks the stress-induced phosphorylation of the scaffold protein SAP97, which is a physiological substrate of SAPK3/p38γ. BIRB796 blocks JNK1/2 activation and activity in HEK293 cells, while not inhibits the activation and activity of ERK1/ERK2 in Hela cells. Moreover, the binding of BIRB796 to the p38 MAPKs or JNK1/2 is impairing their phosphorylation by the upstream kinase MKK6 or MKK4 rather than enhancing their dephosphorylation. BIRB 796 blocks baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. BIRB 796 downregulates IL-6 and VEGF secretion in BMSCs triggered by TNF-α and TGF-β1. BIRB-796 has a pyrazole scaffold that places a lipophilic t-butyl group into the lower selectivity site and a tolyl ring into the upper selectivity site. BIRB-796 also inhibits B-Raf and Abl with IC50 of 83?nM and 14.6?μM, respectively.

体内研究:BIRB 796 (30 mg/kg) inhibits 84% of TNF-α in LPS-stimulated mice and demonstrates efficacy in a mouse model of established collagen-induced arthritis. BIRB 796 has good pharmacokinetic performance even after oral administration in mice.

产品信息订购:

产品更多信息请进入爱必信网站咨询