Home MAPK p38 MAPK inhibitor - JNK inhibitor - Raf inhibitor - Src inhibitor Doramapimod (BIRB 796) For research use only.

Doramapimod (BIRB 796)

Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with Kd of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.

Doramapimod (BIRB 796) Chemical Structure

Doramapimod (BIRB 796) Chemical Structure

CAS No. 285983-48-4

Purity & Quality Control

Doramapimod (BIRB 796) Related Products

Signaling Pathway

p38 MAPK Signaling Pathways

p38 MAPK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HOP-92 Growth Inhibition Assay IC50=24.3838 μM SANGER
NCI-H2228 Growth Inhibition Assay IC50=23.6668 μM SANGER
CAPAN-1 Growth Inhibition Assay IC50=22.1884 μM SANGER
SK-MEL-1 Growth Inhibition Assay IC50=20.3683 μM SANGER
DB Growth Inhibition Assay IC50=18.7923 μM SANGER
AN3-CA Growth Inhibition Assay IC50=18.1 μM SANGER
EW-13 Growth Inhibition Assay IC50=17.9516 μM SANGER
LC-2-ad Growth Inhibition Assay IC50=17.4366 μM SANGER
ES8 Growth Inhibition Assay IC50=17.167 μM SANGER
NCI-H1581 Growth Inhibition Assay IC50=17.0447 μM SANGER
HMV-II Growth Inhibition Assay IC50=14.2309 μM SANGER
BEN Growth Inhibition Assay IC50=13.1264 μM SANGER
NBsusSR Growth Inhibition Assay IC50=10.8235 μM SANGER
MS-1 Growth Inhibition Assay IC50=10.8235 μM SANGER
BFTC-905 Growth Inhibition Assay IC50=10.1233 μM SANGER
NCI-SNU-1 Growth Inhibition Assay IC50=9.06739 μM SANGER
MPP-89 Growth Inhibition Assay IC50=8.46251 μM SANGER
T-24 Growth Inhibition Assay IC50=8.40673 μM SANGER
KP-N-YN Growth Inhibition Assay IC50=8.2019 μM SANGER
IST-MES1 Growth Inhibition Assay IC50=7.95637 μM SANGER
NCI-H358 Growth Inhibition Assay IC50=7.538 μM SANGER
GOTO Growth Inhibition Assay IC50=6.39161 μM SANGER
DU-145 Growth Inhibition Assay IC50=3.93811 μM SANGER
EoL-1-cell Growth Inhibition Assay IC50=0.34763 μM SANGER
KYSE-270 Growth Inhibition Assay IC50=24.5573 μM SANGER
HCC1806 Growth Inhibition Assay IC50=24.7799 μM SANGER
HuO-3N1 Growth Inhibition Assay IC50=25.8185 μM SANGER
HOS Growth Inhibition Assay IC50=25.9292 μM SANGER
KYSE-510 Growth Inhibition Assay IC50=26.1612 μM SANGER
COLO-741 Growth Inhibition Assay IC50=26.3329 μM SANGER
H-EMC-SS Growth Inhibition Assay IC50=26.9245 μM SANGER
HCC1937 Growth Inhibition Assay IC50=27.2238 μM SANGER
NCI-H2126 Growth Inhibition Assay IC50=27.3975 μM SANGER
NCI-H1703 Growth Inhibition Assay IC50=28.0413 μM SANGER
U-2-OS Growth Inhibition Assay IC50=28.5515 μM SANGER
DBTRG-05MG Growth Inhibition Assay IC50=28.5651 μM SANGER
MHH-ES-1 Growth Inhibition Assay IC50=31.941 μM SANGER
HCC1419 Growth Inhibition Assay IC50=32.1119 μM SANGER
HOP-62 Growth Inhibition Assay IC50=32.2701 μM SANGER
AM-38 Growth Inhibition Assay IC50=32.9931 μM SANGER
NCI-H2009 Growth Inhibition Assay IC50=33.4007 μM SANGER
EM-2 Growth Inhibition Assay IC50=33.5511 μM SANGER
SW1116 Growth Inhibition Assay IC50=34.4838 μM SANGER
SK-N-AS Growth Inhibition Assay IC50=35.0714 μM SANGER
ChaGo-K-1 Growth Inhibition Assay IC50=35.6032 μM SANGER
RT-112 Growth Inhibition Assay IC50=35.9879 μM SANGER
HTC-C3 Growth Inhibition Assay IC50=36.2355 μM SANGER
SK-NEP-1 Growth Inhibition Assay IC50=36.6106 μM SANGER
LB831-BLC Growth Inhibition Assay IC50=37.6541 μM SANGER
CTB-1 Growth Inhibition Assay IC50=38.4512 μM SANGER
MOLT-4 Growth Inhibition Assay IC50=38.8391 μM SANGER
SW756 Growth Inhibition Assay IC50=40.9385 μM SANGER
CAL-72 Growth Inhibition Assay IC50=42.03 μM SANGER
KNS-62 Growth Inhibition Assay IC50=42.6296 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
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
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
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with Kd of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.
Features The first p38 MAPK inhibitor to be tested in a phase III clinical trial.
Targets
JNK2 [1] c-RAF [1] Fyn [1] p38α [1]
(Cell-free assay)		 p38α [7]
0.1 nM(Kd) 38 nM
In vitro
In vitro

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. [1]

BIRB 796 potently inhibits c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. [2]

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. [3]

BIRB 796 blocks baseline and 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. [4]

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. [5]
Kinase Assay Procedures for the THP-1 cellular assay for inhibition of LPS-stimulated TNF-α production
THP-1 cells are preincubated in the presence and absence of BIRB 796 for 30 min. Cell mixture is stimulated with LPS (1 μg/mL final) and incubation continued overnight (18−24 hours) as above. Supernatant is analyzed for human TNF-α by a commercially available ELISA. Data are combined and analyzed by nonlinear regression using a three parameter logistic model to obtain an EC50 value. BIRB 796 is analyzed in each experiment and the 95% confidence intervals for the EC50 are between 16 and 22 nM.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-p38 / γ-H2AX mTOR / p-S6K / S6K / p-MK2 / MK2 / p-Hsp27 / Hsp27 p-p38 / p38 27082306
In Vivo
In vivo

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. [1]

BIRB 796 has good pharmacokinetic performance even after oral administration in mice. [2]
Animal Research Animal Models Collagen-induced arthritis in female Balb/c mice
Dosages 1 mg/kg (intravenous) or 10 mg/kg (oral)
Administration Intravenous injection or by oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02211885 Completed
Healthy
Boehringer Ingelheim
 October 2002 Phase 1

Chemical Information & Solubility

Molecular Weight 527.66 Formula

C31H37N5O3
CAS No. 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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (189.51 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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