Adezmapimod (SB203580)

Adezmapimod (SB203580, RWJ 64809, PB 203580) is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM. SB203580 induces mitophagy and autophagy.

CAS No. 152121-47-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
25mg	JPY 22000	国内在庫あり
1g	JPY 145500	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

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製品安全説明書

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Adezmapimod (SB203580)関連製品

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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	Concentration	Incubation Time	活性情報	PMID
RAW 264.7	Cytotoxic Assay	12.5 μM	12h	Blocks lethal toxin-mediated cytotoxicity	17485504
PC12	Kinase Assay	10 μM	15 min	Inhibits p38 MAP kinase with IC50 of 0.6 μM	7750577
HCA2	Function Assay	2.5 μM		Inhibits p38 mediated MK2 activation	17964780
PC12	Function Assay	10 μM		Activates Nrf2/ARE in rat PC12 cells assessed as HO-1 protein induction	21345685
hESCs	Growth Inhibition Assay	5 μM		Induces cardiomyogenic activity assessed as cell growth	23602399
RAW264.7	Function Assay	10 μM		Induces antiinflammatory activity by inhibiting IL-1β release	23791078
RAW264.7	Function Assay	10 μM		Induces antiinflammatory activity by inhibiting iNOS release	23791078
RAW264.7	Function Assay	10 μM		Induces antiinflammatory activity by inhibiting NO release	23791078
RAW264.7	Function Assay	10 μM		Inhibits LPS-induced p38 MAPK phosphorylation	24016057
IEC-18	Function Assay	10 μM		Inhibits LPS-induced p38 MAPK phosphorylation	23758110
whole blood cell	Function assay	0.01 to 100 uM		Inhibition of p38-related IL1-beta release by whole blood cells at 10 e-4 to 10 e-8 M, IC50 = 0.35 μM.	12852754
whole blood cell	Function assay	0.01 to 100 uM		Inhibition of p38-related TNF-alpha release by whole blood cells at 10 e-4 to 10 e-8 M, IC50 = 0.94 μM.	12852754
WS	Function assay	2.5 uM		Inhibition of anisomycin-induced P38-alpha activation in human human TERT-immortalised WS cells assessed as HSP27 phosphorylation at 2.5 uM	17659871
SW1353	Function Assay		1 h	Inhibits IL-6 production with IC50 of 0.05 μM	11140741
PBMC	Function Assay		15 min	Inhibits the release of interleukin-1-beta with IC50 of 0.037 μM	12361396
Sf9	Function assay		30 mins	Inhibition of full-length FLAG-6His-TEV tagged human RIP2 expressed in Sf9 cells assessed as reduction in autophosphorylation pre-incubated for 30 mins followed by incubation with ATP for 2 hrs by ADP-Glo assay, IC50 = 0.01 μM.	26455654
BMDC	Antiinflammatory assay		1 hr	Antiinflammatory activity in C57BL/6 mouse BMDC cells assessed as inhibition of LPS-induced IL-6 production preincubated for 1 hr prior to LPS-stimulation measured after 18 hrs by ELISA, IC50 = 3.5 μM.	24047259
BMDC	Antiinflammatory assay		1 hr	Antiinflammatory activity in C57BL/6 mouse BMDC cells assessed as inhibition of LPS-induced IL-12 p40 production preincubated for 1 hr prior to LPS-stimulation measured after 18 hrs by ELISA, IC50 = 5 μM.	24047259
BMDC	Antiinflammatory assay		1 hr	Antiinflammatory activity in C57BL/6 mouse BMDC cells assessed as inhibition of LPS-induced TNFalpha production preincubated for 1 hr prior to LPS-stimulation measured after 18 hrs by ELISA, IC50 = 7.5 μM.	24047259
macrophage-like cell	Antiinflammatory assay		30 mins	Antiinflammatory activity in human HL-60 derived macrophage-like cells assessed as inhibition of LPS-induced TNFalpha production treated 30 mins before LPS stimulation measured after 24 hrs by ELISA, IC50 = 8.6 μM.	23811089
U937	Function Assay			Inhibits JAK-mediated interferon-gamma/anisomycin-induced Stat1 phosphorylation	18157122
Hela	Function Assay			Inhibits Tat-induced HIV1 LTR transactivation in human HeLa cells with IC50 of 0.1 μM	18926711
THP-1	Function Assay			Inhibits LPS-induced TNFalpha production with IC50 of 0.16 μM	18325768
U937	Function Assay			Inhibits JAK-mediated interferon-gamma/anisomycin-induced p38 phosphorylation	18157122
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 = 0.0217 μM.	28834431
PBMC	Function assay			Inhibition of TNF-alpha production by lipopolysaccharide-stimulated human peripheral blood mononuclear cells, IC50 = 0.025 μM.	9873730
PBMC	Function assay			Inhibition of LPS-stimulated TH+NF-alphs production by human peripheral blood mononuclear cells (PBMCs), IC50 = 0.025 μM.	9784093
PBMC	Function assay			Inhibition of p38 MAP kinase related TNF-alpha release from peripheral blood mononuclear cells (PBMC), IC50 = 0.037 μM.	12061876
PBMC	Function assay			Inhibition of LPS-induced IL1-beta production in human peripheral blood mononuclear cells(PBMCs), IC50 = 0.048 μM.	9784093
SW1353	Function assay			Compound was evaluated for its ability to inhibit IL-6 production in SW1353 cells treated with cytokines IL-1 and TNF, IC50 = 0.05 μM.	10999467
SW1353	Function assay			Inhibition of TNF and IL-1 induced IL-6 production in human chondro-sarcoma SW 1353 cells, IC50 = 0.05 μM.	10999468
THP1	Function assay			Inhibition of LPS-stimulated IL1 production in human THP1 cells, IC50 = 0.05 μM.	18077363
THP1	Function assay			Inhibition of LPS-stimulated TNFalpha production in human THP1 cells, IC50 = 0.05 μM.	18077363
THP1	Function assay			Inhibition of LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in THP-1 cells, EC50 = 0.06 μM.	12086485
THP1	Function assay			Inhibition of tumor necrosis factor alpha release by THP-1 cells, IC50 = 0.07 μM.	15658855
monocytic cell	Function assay			Inhibitory activity against TNF-alpha production using lipopolysaccharide stimulated human monocytic cells, IC50 = 0.072 μM.	12729637
THP1	Function assay			Inhibitory activity against LPS-stimulated TNF-alpha production in human monocytic cells (THP-1), IC50 = 0.072 μM.	15139749
THP-1	Function assay			Inhibitory activity against lipopolysaccharide stimulated TNF-alpha production in THP-1 cells (human monocytic cells), IC50 = 0.072 μM.	15837310
THP1	Function assay			Inhibition of LPS-stimulated TNFalpha production in THP1 cells, IC50 = 0.072 μM.	16750367
PBMC	Function assay			Inhibition of staphylococcal enterotoxin B(SEB) stimulated tumor necrosis factor alpha (TNF-alpha) production by human peripheral blood mononuclear cells(PBMCs), IC50 = 0.16 μM.	9784093
PBMC	Function assay			Concentration required to inhibit lipopolysaccharide induced TNF-alpha release was determined in human peripheral blood mononuclear cells, IC50 = 0.19 μM.	15454231
Sf9	Function assay			Inhibition of full-length FLAG-6His-TEV tagged human RIP2 expressed in Sf9 cells by fluorescent polarization assay, IC50 = 0.2 μM.	26455654
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 = 0.22 μM.	29541362
HEK-293	Function assay			Inhibition of RIP2K in MDP-stimulated HEK-293 cells over-expressing NOD2 assessed as IL8 secretion, IC50 = 0.25 μM.	27109867
PBMC	Function assay			Inhibition of p38 MAP kinase related TNF-alpha release from peripheral blood mononuclear cells (PBMC), IC50 = 0.59 μM.	12061876
PBMC	Function assay			Inhibition of the release of tumor necrosis factor alpha from peripheral blood mononuclear cells, IC50 = 0.59 μM.	12361396
PBMC	Function assay			Inhibitory activity against TNF-alpha release in PBM cells, IC50 = 0.59 μM.	12852754
HEK-293	Function assay			Inhibition of RIP2K in Pam2CSK4-stimulated HEK-293 cells over-expressing TLR2 assessed as IL8 secretion, IC50 = 6.31 μM.	27109867
WS	Function assay			Inhibition of MK2 mediated HSP27 phosphorylation in immortalised WS cells assessed as reduction in F-actin stress fibres	17964780
WS	Function assay			Inhibition of p38 mediated MK2 activation in WS cells	17964780
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 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

Adezmapimod (SB203580, RWJ 64809, PB 203580) is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM. SB203580 induces mitophagy and autophagy.

特性

First reported p38 inhibitor.

Targets

p38 MAPK ^[1] (THP-1 cells)	PKB ^[1] (THP-1 cells)
0.3 μM-0.5 μM	3 μM-5 μM

In Vitro
In vitro	SB203580 inhibits the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells with an IC50 of 3–5 μm. SB203580 also inhibits IL-2-induced p70S6 kinase activation, although the concentration required is slightly higher with an IC50 above 10 μm. SB203580 also inhibits the activity of PDK1 in a dose-dependent manner with an IC50 in the 3–10 μm range. ^[1] SB203580 inhibits p38-MAPK stimulation of MAPKAPK2 with an IC50 of approximately 0.07 μM, whereas inhibits total SAPK/JNK activity with an IC50 of 3–10 μM. SB203580 at higher concentrations activates the ERK pathway, which subsequently enhances NF-κB transcriptional activity. ^[2] SB203580 induces autophagy in human hepatocellular carcinoma (HCC) cells. ^[3]
Kinase Assay	Cellular receptor kinase phosphorylation assay
Kinase Assay	4 μg of sheep anti-PKBα is immobilized on 25 μL of protein G-Sepharose overnight (or 1.5 hours) and washed in Buffer A (50 mm Tris, pH 7.5, 1 mm EDTA, 1 mm EGTA, 0.5 mm Na₃VO₄, 0.1% β-mercaptoethanol, 1% Triton X-100, 50 mm sodium fluoride, 5 mm sodium pyrophosphate, 0.1 mm phenylmethylsulfonyl fluoride, 1 μg/mL aprotinin, pepstatin, leupeptin, and 1 μm microcystin). The immobilized anti-PKB is then incubated with 0.5 ml of lysate (from 5 × 10⁶ cells) for 1.5 hours and washed three times in 0.5 mL of Buffer A supplemented with 0.5 m NaCl, two times in 0.5 mL of Buffer B (50 mm Tris-HCl, pH 7.5, 0.03% (w/v) Brij-35, 0.1 mm EGTA, and 0.1% β-mercaptoethanol), and twice with 100 μl of assay dilution buffer; 5× assay dilution buffer is 100 mm MOPS, pH 7.2, 125 mm β-glycerophosphate, 25 mm EGTA, 5 mm sodium orthovanadate, 5 mm DTT. To the PKB enzyme immune complex is added 10 μL of assay dilution buffer, 40 μm protein kinase A inhibitor peptide, 100 μm PKB-specific substrate peptide, and 10 μCi of [γ-³²P]ATP, all made up in assay dilution buffer. The reaction is incubated for 20 minutes at room temperature with shaking, then samples are pulse spun, and 40 μL of reaction volume are removed into another tube to which is added 20 μL of 40% trichloroacetic acid to stop the reaction. This is mixed and incubated for 5 minutes at room temperature, and 40 μL is transferred onto P81 phosphocellulose paper and allowed to bind for 30 seconds. The P81 piece is washed three times in 0.75% phosphoric acid then in acetone at room temperature. γ-³²P incorporation is then measured by scintillation counting.
細胞実験	細胞株	CT6 cell , BA/F3 F7 cell
	濃度	0–30 μM
	反応時間	1 hour
	実験の流れ	CT6 cell and BA/F3 F7 cell are rested by washing three times in RPMI and culturing overnight in RPMI, 5% fetal calf serum in the absence of growth factor, antibiotics, or β-mercaptoethanol supplements. 2–5 × 10⁶ rested CT6 cells are resuspended in 2 mL of RPMI, 5% fetal calf serum and preincubated with SB203580 or vehicle control as indicated in figure legends. Cells are then stimulated with 20 ng/ml recombinant human IL-2 for 5 minutes at 37 °C and pelleted in a minifuge for 30 seconds, medium is aspirated, and the pellet is lysed in the appropriate buffer. BA/F3 cells stably expressing deletion mutants of IL-2 receptor β chain are maintained in glutamine containing RPMI further supplemented with 5% fetal calf serum and 0.2 μg/mL G418. The cells are then washed extensively, rested overnight, and washed again before activating with IL-2; such cell preparations are >90% T cells. Cellular proliferation assays are performed by measurement of [³H]thymidine incorporation.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	phospho-p38 / p38 p-ASK1 / ASK1 / P-JNK / p-MKK4 / p-ERK phospho-MK2(T334) / phospho-HSP27(S82) / phospho-Akt(T308) / phospho-Akt(S473)		25747578
	Immunofluorescence	dsRNA / hnRNP A1		25747578
	Growth inhibition assay	Cell viability		23001390

In Vivo
In Vivo	SB203580 protects pig myocardium against ischemic injury in an in vivo model. ^[4]SB203580 is effective to prevent and treat the disease in MRL/lpr mice model of Systemic lupus erythematosus (SLE). ^[5]
動物実験	動物モデル	Systemic lupus erythematosus (SLE) are established in female MRL/lpr mice and female C57BL/6 mice
	投与量	0.1 M/day
	投与経路	Orally administered

参考
[1] Ferdinand V. Lali, et al. J Biol Chem, 2000, 275(10), 7395-402. [2] Birkenkamp KU, et al. Br J Pharmacol, 2000, 131(1): 99-107. [3] Zhang H, et al. Apoptosis, 2011 [4] Barancik M, et al. J Cardiovasc Pharmacol, 2000, 35(3), 474-83. [5] Jin N, et al. Int Immunopharmacol, 2011, 11(9):1319-26. + 展開

参考

+ 展開

化学情報

分子量	377.43	化学式	C₂₁H₁₆FN₃OS
CAS No.	152121-47-6	SDF	Download Adezmapimod (SB203580) SDFをダウンロードする
Smiles	CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F
保管	3 years-20°C （in the dark）powder	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 years-20°C （in the dark）powder	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 : 38 mg/mL ( (100.68 mM)； Warmed with 50℃ water bath; 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。)

Water : Insoluble

Ethanol : 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):