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)化学構造

CAS No. 285983-48-4

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 44100 国内在庫あり
JPY 22000 国内在庫あり
JPY 70500 国内在庫あり
JPY 220500 国内在庫あり
JPY 595500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール:[email protected]
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Doramapimod (BIRB 796)関連製品

シグナル伝達経路

p38 MAPK阻害剤の選択性比較

Cell Data

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

製品説明 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.
特性 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.
実験結果図 Methods Biomarkers 結果図 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]

動物実験 動物モデル Collagen-induced arthritis in female Balb/c mice
投与量 1 mg/kg (intravenous) or 10 mg/kg (oral)
投与経路 Intravenous injection or by oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02211885 Completed
Healthy
Boehringer Ingelheim
October 2002 Phase 1

化学情報

分子量 527.66 化学式

C31H37N5O3

CAS No. 285983-48-4 SDF Download Doramapimod (BIRB 796) SDFをダウンロードする
Smiles CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5
保管

In vitro
Batch:

DMSO : 100 mg/mL ( (189.51 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 100 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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