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SB203580 (Adezmapimod) p38 MAPK remmer

Name: SB203580 (Adezmapimod)
Brand: Selleck Chemicals
SKU: S1076
Rating: 5 (989 reviews)

Cat.Nr.S1076

Adezmapimod (SB203580, RWJ 64809, PB 203580) is een p38 MAPK-remmer met een IC50 van 0,3-0,5 μM in THP-1-cellen, 10 keer minder gevoelig voor SAPK3(106T) en SAPK4(106T) en blokkeert PKB-fosforylering met een IC50 van 3-5 μM. SB203580 induceert mitophagy en autophagy.

SB203580 (Adezmapimod) p38 MAPK remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 377.43

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Kwaliteitscontrole

Batch: Zuiverheid: 99.98%

99.98

Gerelateerde doelwitten	ERK Raf JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Overige p38 MAPK Inhibitoren	SB202190 PH-797804 Doramapimod (BIRB 796) Ralimetinib (LY2228820) dimesylate VX-702 Losmapimod SB239063 Neflamapimod (VX-745) BMS-582949 Skepinone-L

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
PC12	Kinase Assay	10 μM	15 min		Inhibits p38 MAP kinase with IC50 of 0.6 μM	7750577
THP-1	Function Assay				Inhibits LPS-induced TNFalpha production with IC50 of 0.16 μM	18325768
PBMC	Function Assay		15 min	DMSO	Inhibits the release of interleukin-1-beta with IC50 of 0.037 μM	12361396
SW1353	Function Assay		1 h	DMSO	Inhibits IL-6 production with IC50 of 0.05 μM	11140741
Hela	Function Assay			DMSO	Inhibits Tat-induced HIV1 LTR transactivation in human HeLa cells with IC50 of 0.1 μM	18926711
PC12	Function Assay	10 μM		DMSO	Activates Nrf2/ARE in rat PC12 cells assessed as HO-1 protein induction	21345685
RAW 264.7	Cytotoxic Assay	12.5 μM	12h	DMSO	Blocks lethal toxin-mediated cytotoxicity	17485504
HCA2	Function Assay	2.5 μM			Inhibits p38 mediated MK2 activation	17964780
U937	Function Assay				Inhibits JAK-mediated interferon-gamma/anisomycin-induced Stat1 phosphorylation	18157122
U937	Function Assay				Inhibits JAK-mediated interferon-gamma/anisomycin-induced p38 phosphorylation	18157122
hESCs	Growth Inhibition Assay	5 μM		DMSO	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
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
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
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
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
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
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
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
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
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
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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	377.43	Formule	C₂₁H₁₆FN₃OS	Opslag (Vanaf de ontvangstdatum)	3 years -20°C(in the dark) powder
CAS-nr.	152121-47-6	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	RWJ 64809, PB 203580			Smiles	CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F

Oplosbaarheid

In vitro
Batch:

DMSO : 38 mg/mL (100.68 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5% DMSO 1 40% PEG 300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (13.25mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	First reported p38 inhibitor.
Targets/IC₅₀/Ki	p38 MAPK (THP-1 cells) 0.3 μM-0.5 μM PKB (THP-1 cells) 3 μM-5 μM
In vitro	Adezmapimod (SB203580) remt de IL-2-geïnduceerde proliferatie van primaire menselijke T-cellen, muizen CT6 T-cellen of BAF F7 B-cellen met een IC50 van 3–5 μm. Het remt ook de IL-2-geïnduceerde p70S6 kinase-activering, hoewel de benodigde concentratie iets hoger is met een IC50 boven 10 μm. Deze verbinding remt de activiteit van PDK1 op een dosisafhankelijke manier met een IC50 in het bereik van 3–10 μm. Het remt p38-MAPK-stimulatie van MAPKAPK2 met een IC50 van ongeveer 0,07 μM, terwijl de totale SAPK/JNK-activiteit wordt geremd met een IC50 van 3–10 μM. Bij hogere concentraties activeert het de ERK-route, wat vervolgens de NF-κB transcriptionele activiteit versterkt. Het induceert ook autofagie in menselijke hepatocellulaire carcinoom (HCC) cellen.
Kinase Assay	Cellulaire receptorkinase fosforyleringsanalyse
Kinase Assay	4 μg schaap anti-PKBα wordt 's nachts (of 1,5 uur) geïmmobiliseerd op 25 μL proteïne G-Sepharose en gewassen in Buffer A (50 mm Tris, pH 7,5, 1 mm EDTA, 1 mm EGTA, 0,5 mm Na₃VO₄, 0,1% β-mercapto-ethanol, 1% Triton X-100, 50 mm natriumfluoride, 5 mm natriumpyrofosfaat, 0,1 mm fenylmethylsulfonylfluoride, 1 μg/mL pepstatine, leupeptine en 1 μm microcystine). De geïmmobiliseerde anti-PKB wordt vervolgens geïncubeerd met 0,5 ml lysaat (van 5 × 10⁶ cellen) gedurende 1,5 uur en driemaal gewassen in 0,5 ml Buffer A aangevuld met 0,5 m NaCl, tweemaal in 0,5 ml Buffer B (50 mm Tris-HCl, pH 7,5, 0,03% (w/v) Brij-35, 0,1 mm EGTA en 0,1% β-mercapto-ethanol), en tweemaal met 100 μl assay verdunningsbuffer; 5× assay verdunningsbuffer is 100 mm MOPS, pH 7,2, 125 mm β-glycerofosfaat, 25 mm EGTA, 5 mm natriumorthovanadaat, 5 mm DTT. Aan het PKB-enzym immuuncomplex wordt 10 μL assay verdunningsbuffer, 40 μm proteïne kinase A-remmer peptide, 100 μm PKB-specifiek substraatpeptide en 10 μCi [γ-³²P]ATP toegevoegd, allemaal opgemaakt in assay verdunningsbuffer. De reactie wordt 20 minuten bij kamertemperatuur geïncubeerd onder schudden, waarna monsters worden gepulst en 40 μL van het reactievolume wordt overgebracht naar een andere buis waaraan 20 μL 40% trichloorazijnzuur wordt toegevoegd om de reactie te stoppen. Dit wordt gemengd en 5 minuten bij kamertemperatuur geïncubeerd, en 40 μL wordt overgebracht op P81 fosfocellulosepapier en 30 seconden laten binden. Het P81-stuk wordt driemaal gewassen in 0,75% fosforzuur en vervolgens in aceton bij kamertemperatuur. γ-³²P-incorporatie wordt vervolgens gemeten door scintillatietelling.
In vivo	Adezmapimod (SB203580) beschermt varkensmyocard tegen ischemische schade in een in vivo model. Het is ook effectief in het voorkomen en behandelen van de ziekte in het MRL/lpr muizenmodel van systemische lupus erythematosus (SLE).
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/10702313/ [2] https://pubmed.ncbi.nlm.nih.gov/10960075/ [3] https://pubmed.ncbi.nlm.nih.gov/22170404/ [4] https://pubmed.ncbi.nlm.nih.gov/10710135/ [5] https://pubmed.ncbi.nlm.nih.gov/21549858/

Toepassingen

Methoden	Biomarkers	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

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