Doramapimod_product_DataBase

Bioactivity

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[1][2].

Invitro

Doramapimod (BIRB 796) is usually associated with inflammation because of its role in T-cell proliferation and cytokine production[1]. Doramapimod (BIRB 796) blocks the stress-induced phosphorylation of the scaffold protein SAP97, further establishing that this is a physiological substrate of SAPK3/p38γ. The binding of Doramapimod to the p38 MAPKs or JNK1/2 is impairing their phosphorylation by the upstream kinase MKK6 or MKK4[3].

In Vivo

The mean xenograft weigh of Doramapimod (BIRB 796) is lighter than control. The inhibition rate of Doramapimod is 1.93%[4]. The Doramapimod (BIRB 796) treatment slightly reduces blood pressure (166±7 mm Hg at week 7; P<0.05), whereas SD rats are normotensive (123±3 mm Hg). Despite the reduction in blood pressure, untreated and Doramapimod-treated dTGRs have similar heart weight and cardiac hypertrophy indices (heart-to-tibia ratio), which are significantly higher compare with nontransgenic SD rats (310±6 versus 307±6 versus 206±5 mg/cm, respectively; P<0.05)[5].

Name

Doramapimod

CAS

285983-48-4

Formula

C31H37N5O3

Molar Mass

527.66

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Dietrich J, et al. The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors. Bioorg Med Chem. 2010 Aug 1;18(15):5738-48 [2]. Cicenas J, et al. JNK, p38, ERK, and SGK1 Inhibitors in Cancer. Cancers (Basel). 2017 Dec 21;10(1). pii: E1. [3]. Kuma Y, et al. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem, 2005, 280(20), 19472-19479. [4]. He D, et al. BIRB796, the inhibitor of p38 mitogen-activated protein kinase, enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cells. PLoS One. 2013;8(1):e54181. [5]. Park JK, et al. p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. Hypertension. 2007 Mar;49(3):481-9.

PeptideDB

Doramapimod

CAS: 285983-48-4 F: C31H37N5O3 W: 527.66