产品信息
抗原名称
p38α
商品描述
Doramapimod (BIRB 796) is an orally active, highly potent p38 MAPK inhibitor, which has an IC50 for p38α=38 nM, for p38β=65 nM, for p38γ=200 nM, and for p38δ=520 nM. Doramapimod has picomolar affinity for p38 kinase (Kd=0.1 nM). Doramapimod also inhibits B-Raf with an IC50 of 83 nM.
分子量
527.66
纯度
＞98%
可溶性
DMSO : 125 mg/mL (236.89 mM; Need ultrasonic)
Ethanol : 33.33 mg/mL (63.17 mM; Need ultrasonic)
Ethanol : 33.33 mg/mL (63.17 mM; Need ultrasonic)
外观
White or off-white solid
In vitro(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.
In vivo(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.
背景
别名
达马莫德
分子式
C31H37N5O3
CAS号
285983-48-4
制备和贮存
保存方式
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
参考图片
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