BIRB 796 (Doramapimod)

Catalog No.S1574

BIRB 796 (Doramapimod) 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.

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BIRB 796 (Doramapimod) Chemical Structure

BIRB 796 (Doramapimod) Chemical Structure
Molecular Weight: 527.66

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Related Compound Libraries

BIRB 796 (Doramapimod) is available in the following compound libraries:

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Product Information

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  • Research Area
  • BIRB 796 (Doramapimod) Mechanism

Product Description

Biological Activity

Description BIRB 796 (Doramapimod) 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.
Targets p38α [1]
(Cell-free assay)
p38α [7]
IC50 0.1 nM(Kd) 38 nM
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 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. [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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
EoL-1-cellMkLvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M3HvS2lEPTB;MD6zOFc3OyEQvF2=NHzZeVVUSU6JUlXS
DU-145NW[3blM4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoTFTWM2OD1|LkmzPFEyKM7:TR?=MV7TRW5IWkWU
GOTONGD2OFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoX1TWM2OD14LkO5NVYyKM7:TR?=NF\afWlUSU6JUlXS
NCI-H358NVuwelBVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mk\JTWM2OD15LkWzPEDPxE1?MXXTRW5IWkWU
IST-MES1NYPSVWNtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXPlVXhOUUN3ME23Mlk2PjN5IN88US=>M3y1fXNCVkeURWK=
KP-N-YNNGLGTlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1XOdWlEPTB;OD6yNFE6KM7:TR?=NF3FXZNUSU6JUlXS
T-24M4nOV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWr4boRXUUN3ME24MlQxPjd|IN88US=>M3jjfHNCVkeURWK=
MPP-89NF;lZZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MW\JR|UxRThwNE[yOVEh|ryPNWrTVmFoW0GQR2LFVi=>
NCI-SNU-1M1\HNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NY\vZmE{UUN3ME25MlA3PzN7IN88US=>M120fnNCVkeURWK=
BFTC-905NYfnOW1[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUnYTIhIUUN3ME2xNE4yOjN|IN88US=>M{T5XnNCVkeURWK=
MS-1NEf6fGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmHOTWM2OD1zMD64NlM2KM7:TR?=NW\NVJZ1W0GQR2LFVi=>
NBsusSRNET4[2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYnwfYNFUUN3ME2xNE45OjN3IN88US=>Ml3vV2FPT1KHUh?=
BENNVTCbVJsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVHJR|UxRTF|LkGyOlQh|ryPMYDTRW5IWkWU
HMV-IINIWzN2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGXKOlRKSzVyPUG0MlI{ODlizszNMWPTRW5IWkWU
NCI-H1581NYr1NW9FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MX\JR|UxRTF5LkC0OFch|ryPMXfTRW5IWkWU
ES8M4Xn[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1W0[WlEPTB;MUeuNVY4KM7:TR?=MnSyV2FPT1KHUh?=
LC-2-adNVTNfHk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoHHTWM2OD1zNz60N|Y3KM7:TR?=M{XLTXNCVkeURWK=
EW-13MmnKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXrJR|UxRTF5Lkm1NVYh|ryPNVnZdlBKW0GQR2LFVi=>
AN3-CAMoPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWrJR|UxRTF6LkGg{txOMWHTRW5IWkWU
DBMXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mme3TWM2OD1zOD63PVI{KM7:TR?=NWCwOJJyW0GQR2LFVi=>
SK-MEL-1MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFPZTmRKSzVyPUKwMlM3QDNizszNNWXseItoW0GQR2LFVi=>
CAPAN-1MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYLJR|UxRTJ{LkG4PFQh|ryPNVfqbmw{W0GQR2LFVi=>
NCI-H2228MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGHUbZBKSzVyPUKzMlY3PjhizszNNXnhO5F6W0GQR2LFVi=>
HOP-92MlzIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MofZTWM2OD1{ND6zPFM5KM7:TR?=Mk\vV2FPT1KHUh?=
KYSE-270NV\rd4RRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVrJR|UxRTJ2LkW1O|Mh|ryPMVfTRW5IWkWU
HCC1806MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFHOWGdKSzVyPUK0Mlc4QTlizszNNWK1VHhMW0GQR2LFVi=>
HuO-3N1MmLPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHnZRYVKSzVyPUK1MlgyQDVizszNNWnuPGxHW0GQR2LFVi=>
HOSNEjX[lJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYrJR|UxRTJ3LkmyPVIh|ryPM2THTHNCVkeURWK=
KYSE-510M3zzcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1fIR2lEPTB;Mk[uNVYyOiEQvF2=NWHlZ3E6W0GQR2LFVi=>
COLO-741MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVz5TVFoUUN3ME2yOk4{OzJ7IN88US=>Moj4V2FPT1KHUh?=
H-EMC-SSM1LvSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYr0bGZrUUN3ME2yOk46OjR3IN88US=>MoLZV2FPT1KHUh?=
HCC1937NIjqPHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoDlTWM2OD1{Nz6yNlM5KM7:TR?=MUjTRW5IWkWU
NCI-H2126MofmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYfUTWdLUUN3ME2yO{4{QTd3IN88US=>NVHzS3BOW0GQR2LFVi=>
NCI-H1703MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4i2UGlEPTB;MkiuNFQyOyEQvF2=MoXKV2FPT1KHUh?=
U-2-OSMVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlrUTWM2OD1{OD61OVE2KM7:TR?=NVqxUmtjW0GQR2LFVi=>
DBTRG-05MGMlnLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MlTaTWM2OD1{OD61OlUyKM7:TR?=NEPpUphUSU6JUlXS
MHH-ES-1NULXUnRoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MX3JR|UxRTNzLkm0NUDPxE1?MX\TRW5IWkWU
HCC1419NIfqOlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NI\zVFFKSzVyPUOyMlEyOTlizszNMVPTRW5IWkWU
HOP-62NYm3TWtCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2\5S2lEPTB;M{KuNlcxOSEQvF2=NGHlTlBUSU6JUlXS
AM-38MkL4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NEC0WodKSzVyPUOyMlk6OzFizszNNV25SHlbW0GQR2LFVi=>
NCI-H2009NEW3c49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MX3JR|UxRTN|LkSwNFch|ryPNX7ONndpW0GQR2LFVi=>
EM-2M1e0U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGfseZFKSzVyPUOzMlU2OTFizszNNEX3OnlUSU6JUlXS
SW1116NXfOWlhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnzaTWM2OD1|ND60PFM5KM7:TR?=NIO1clNUSU6JUlXS
SK-N-ASMYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1e3V2lEPTB;M{WuNFcyPCEQvF2=M323bnNCVkeURWK=
ChaGo-K-1M1\MSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NIfqWWNKSzVyPUO1MlYxOzJizszNNVy2dXgyW0GQR2LFVi=>
RT-112NWizS245T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{Xh[2lEPTB;M{WuPVg4QSEQvF2=NX\tTGp1W0GQR2LFVi=>
HTC-C3NFfpPFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1L6N2lEPTB;M{[uNlM2PSEQvF2=MoLVV2FPT1KHUh?=
SK-NEP-1NFzhWWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWGy[ZJTUUN3ME2zOk43OTB4IN88US=>M1OydXNCVkeURWK=
LB831-BLCMYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWjJR|UxRTN5Lk[1OFEh|ryPNHixXYFUSU6JUlXS
CTB-1MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYjOVGo1UUN3ME2zPE41PTF{IN88US=>M16ycXNCVkeURWK=
MOLT-4NXrEdXdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmPvTWM2OD1|OD64N|kyKM7:TR?=NGSzclJUSU6JUlXS
SW756MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1PaXGlEPTB;NECuPVM5PSEQvF2=MW\TRW5IWkWU
CAL-72MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWPJR|UxRTR{LkCzJO69VQ>?MWPTRW5IWkWU
KNS-62MljFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MV3JR|UxRTR{Lk[yPVYh|ryPMoDFV2FPT1KHUh?=
KARPAS-299M4jZdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M{nyXWlEPTB;NEOuN|I{OyEQvF2=MkDIV2FPT1KHUh?=
HELNVzxd3ZKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4DqVmlEPTB;NEWuOFY1PiEQvF2=NUXpTIM1W0GQR2LFVi=>
KP-4MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlG3TWM2OD12Nj63N|YyKM7:TR?=MkjLV2FPT1KHUh?=
NEC8M3PwNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MVvJR|UxRTR5LkG2OlEh|ryPMWrTRW5IWkWU
G-402NVOwNW1nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX7QdVdWUUN3ME20PE44ODF{IN88US=>M3mxN3NCVkeURWK=

... Click to View More Cell Line Experimental Data

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]
Features The first p38 MAPK inhibitor to be tested in a phase III clinical trial.

Protocol(Only for Reference)

Kinase Assay:

[6]

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.

Animal Study:

[2]

Animal Models Collagen-induced arthritis in female Balb/c mice
Formulation 70% PEG400 (intravenous) or 100% PEG400 (oral)
Dosages 1 mg/kg (intravenous) or 10 mg/kg (oral)
Administration Intravenous injection or by oral

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Pargellis C, et al. Nat Struct Biol, 2002, 9(4), 268-272.

[2] Regan J, et al. J Med Chem, 2002, 45(14), 2994-3008.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02214888 Terminated Arthritis, Rheumatoid Boehringer Ingelheim May 2003 Phase 2
NCT02211885 Completed Healthy Boehringer Ingelheim October 2002 Phase 1
NCT02209753 Completed Psoriasis Boehringer Ingelheim June 2001 Phase 2
NCT02209805 Completed Healthy Boehringer Ingelheim January 2001 Phase 1

Chemical Information

Download BIRB 796 (Doramapimod) SDF
Molecular Weight (MW) 527.66
Formula

C31H37N5O3

CAS No. 285983-48-4
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 106 mg/mL (200.88 mM)
Ethanol 106 mg/mL (200.88 mM)
Water <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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