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 K_d 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.

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
5mg	JPY 22000	国内在庫あり
50mg	JPY 70500	国内在庫あり
200mg	JPY 220500	国内在庫あり
1g	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] よく尋ねられる質問

文献中Selleckの製品使用例（115）

製品安全説明書

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Doramapimod (BIRB 796)関連製品

関連ターゲット	p38α p38β	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library MAPK Inhibitor Library Cell Cycle compound library TGF-beta/Smad compound library Anti-alzheimer Disease Compound Library	もっと見る

シグナル伝達経路

p38 MAPK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	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 K_d 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 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]
Kinase Assay	Procedures for the THP-1 cellular assay for inhibition of LPS-stimulated TNF-α production
Kinase Assay	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
実験結果図	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
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT02211885	Completed	Healthy	Boehringer Ingelheim	October 2002	Phase 1

参考
[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. [3] Kuma Y, et al. J Biol Chem, 2005, 280(20), 19472-19479. [4] Yasui H, et al. Br J Haematol, 2007, 136(3), 414-423. [5] Dietrich J, et al. Bioorg Med Chem. 2010, 18(15), 5738-5748. [6] Regan J, et al. J Med Chem, 2003, 46(22), 4676-4686. + 展開

参考

+ 展開

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	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

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
=	×	×

希釈計算器分子量計算器

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）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

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。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):