alleen voor onderzoeksdoeleinden

VX-702 p38 MAPK remmer

Name: VX-702
Brand: Selleck Chemicals
SKU: S6005
Rating: 5 (42 reviews)

Cat.nr.S6005

VX-702 is een zeer selectieve remmer van p38α MAPK, met een 14-voudig hogere potentie tegen p38α versus p38β.

VX-702 p38 MAPK remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 404.3

Spring naar

Kwaliteitscontrole

Batch: Zuiverheid: 99.94%

99.94

Gerelateerde doelwitten	ERK Raf JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Overig p38 MAPK Inhibitoren	SB202190 SB203580 (Adezmapimod) PH-797804 Doramapimod (BIRB 796) Ralimetinib (LY2228820) dimesylate Losmapimod SB239063 Neflamapimod (VX-745) BMS-582949 Skepinone-L

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Activiteitsbeschrijving
HOP-62 cell	Growth inhibition assay	Inhibition of human HOP-62 cell growth in a cell viability assay, IC50=0.01543 μM
human NCI-H720 cell	Growth inhibition assay	Inhibition of human NCI-H720 cell growth in a cell viability assay, IC50=0.01682 μM
JVM-2 cell	Growth inhibition assay	Inhibition of human JVM-2 cell growth in a cell viability assay, IC50=0.083 μM
human NCI-H69 cell	Growth inhibition assay	Inhibition of human NCI-H69 cell growth in a cell viability assay, IC50=0.09941 μM
human BV-173 cell	Growth inhibition assay	Inhibition of human BV-173 cell growth in a cell viability assay, IC50=0.11386 μM
human KU812 cell	Growth inhibition assay	Inhibition of human KU812 cell growth in a cell viability assay, IC50=0.12488 μM
human DU-145 cell	Growth inhibition assay	Inhibition of human DU-145 cell growth in a cell viability assay, IC50=0.14554 μM
KARPAS-45 cell	Growth inhibition assay	Inhibition of human KARPAS-45 cell growth in a cell viability assay, IC50=0.14826 μM
human AGS cell	Growth inhibition assay	Inhibition of human AGS cell growth in a cell viability assay, IC50=0.15251 μM
human MOLT-13 cell	Growth inhibition assay	Inhibition of human MOLT-13 cell growth in a cell viability assay, IC50=0.15981 μM
human NCI-H209 cell	Growth inhibition assay	Inhibition of human NCI-H209 cell growth in a cell viability assay, IC50=0.1758 μM
human CTV-1 cell	Growth inhibition assay	Inhibition of human CTV-1 cell growth in a cell viability assay, IC50=0.18389 μM
LU-139 cell	Growth inhibition assay	Inhibition of human LU-139 cell growth in a cell viability assay, IC50=0.19435 μM
ML-2 cell	Growth inhibition assay	Inhibition of human ML-2 cell growth in a cell viability assay, IC50=0.22661 μM
human K5 cell	Growth inhibition assay	Inhibition of human K5 cell growth in a cell viability assay, IC50=0.22917 μM
human SBC-1 cell	Growth inhibition assay	Inhibition of human SBC-1 cell growth in a cell viability assay, IC50=0.2362 μM
human COR-L88 cell	Growth inhibition assay	Inhibition of human COR-L88 cell growth in a cell viability assay, IC50=0.3348 μM
human KY821 cell	Growth inhibition assay	Inhibition of human KY821 cell growth in a cell viability assay, IC50=0.39603 μM
human HCC2218 cell	Growth inhibition assay	Inhibition of human HCC2218 cell growth in a cell viability assay, IC50=0.49728 μM
human ECC10 cell	Growth inhibition assay	Inhibition of human ECC10 cell growth in a cell viability assay, IC50=0.65389 μM
human EW-3 cell	Growth inhibition assay	Inhibition of human EW-3 cell growth in a cell viability assay, IC50=0.66611 μM
human EW-18 cell	Growth inhibition assay	Inhibition of human EW-18 cell growth in a cell viability assay, IC50=0.74679 μM
human UACC-257 cell	Growth inhibition assay	Inhibition of human UACC-257 cell growth in a cell viability assay, IC50=1.20326 μM
human G-361 cell	Growth inhibition assay	Inhibition of human G-361 cell growth in a cell viability assay, IC50=1.49519 μM
human HMV-II cell	Growth inhibition assay	Inhibition of human HMV-II cell growth in a cell viability assay, IC50=1.77184 μM
human DEL cell	Growth inhibition assay	Inhibition of human DEL cell growth in a cell viability assay, IC50=2.20704 μM
human IGROV-1 cell	Growth inhibition assay	Inhibition of human IGROV-1 cell growth in a cell viability assay, IC50=2.43188 μM
human SK-OV-3 cell	Growth inhibition assay	Inhibition of human SK-OV-3 cell growth in a cell viability assay, IC50=2.61697 μM
human LAMA-84 cell	Growth inhibition assay	Inhibition of human LAMA-84 cell growth in a cell viability assay, IC50=2.71284 μM
human NCI-H510A cell	Growth inhibition assay	Inhibition of human NCI-H510A cell growth in a cell viability assay, IC50=2.92526 μM
human CP66-MEL cell	Growth inhibition assay	Inhibition of human CP66-MEL cell growth in a cell viability assay, IC50=2.93559 μM
human HAL-01 cell	Growth inhibition assay	Inhibition of human HAL-01 cell growth in a cell viability assay, IC50=3.27918 μM
human RS4-11 cell	Growth inhibition assay	Inhibition of human RS4-11 cell growth in a cell viability assay, IC50=3.70573 μM
human RPMI-8226 cell	Growth inhibition assay	Inhibition of human RPMI-8226 cell growth in a cell viability assay, IC50=3.82376 μM
human NCI-H82 cell	Growth inhibition assay	Inhibition of human NCI-H82 cell growth in a cell viability assay, IC50=3.89305 μM
human NY cells	Growth inhibition assay	Inhibition of human NY cell growth in a cell viability assay, IC50=4.27637 μM
human MDA-MB-361 cell	Growth inhibition assay	Inhibition of human MDA-MB-361 cell growth in a cell viability assay, IC50=4.43158 μM
human MOLT-4 cell	Growth inhibition assay	Inhibition of human MOLT-4 cell growth in a cell viability assay, IC50=4.99193 μM
human DU-4475 cell	Growth inhibition assay	Inhibition of human DU-4475 cell growth in a cell viability assay, IC50=5.05565 μM
human ESS-1 cell	Growth inhibition assay	Inhibition of human ESS-1 cell growth in a cell viability assay, IC50=5.29179 μM
human NCI-H1299 cell	Growth inhibition assay	Inhibition of human NCI-H1299 cell growth in a cell viability assay, IC50=5.53033 μM
human COLO-684 cell	Growth inhibition assay	Inhibition of human COLO-684 cell growth in a cell viability assay, IC50=5.58165 μM
human MV-4-11 cell	Growth inhibition assay	Inhibition of human MV-4-11 cell growth in a cell viability assay, IC50=5.71199 μM
human D-542MG cell	Growth inhibition assay	Inhibition of human D-542MG cell growth in a cell viability assay, IC50=6.39272 μM
human A4-Fuk cell	Growth inhibition assay	Inhibition of human A4-Fuk cell growth in a cell viability assay, IC50=6.43662 μM
human HL-60 cell	Growth inhibition assay	Inhibition of human HL-60 cell growth in a cell viability assay, IC50=7.52212 μM
human NCI-H526 cell	Growth inhibition assay	Inhibition of human NCI-H526 cell growth in a cell viability assay, IC50=7.59801 μM
human L-363 cell	Growth inhibition assay	Inhibition of human L-363 cell growth in a cell viability assay, IC50=7.79252 μM
human A388 cell	Growth inhibition assay	Inhibition of human A388 cell growth in a cell viability assay, IC50=7.80384 μM
human MS-1	Growth inhibition assay	Inhibition of human MS-1 cell growth in a cell viability assay, IC50=7.83465 μM
human JAR cell	Growth inhibition assay	Inhibition of human JAR cell growth in a cell viability assay, IC50=7.84923 μM
human TI-73 cell	Growth inhibition assay	Inhibition of human TI-73 cell growth in a cell viability assay, IC50=8.0622 μM
human CTB-1 cell	Growth inhibition assay	Inhibition of human CTB-1 cell growth in a cell viability assay, IC50=8.17825 μM
human SK-NEP-1 cell	Growth inhibition assay	Inhibition of human SK-NEP-1 cell growth in a cell viability assay, IC50=11.3038 μM
human HT-29 cell	Growth inhibition assay	Inhibition of human HT-29 cell growth in a cell viability assay, IC50=13.9111 μM
human NCI-H1092 cell	Growth inhibition assay	Inhibition of human NCI-H1092 cell growth in a cell viability assay, IC50=14.318 μM
human KMOE-2 cell	Growth inhibition assay	Inhibition of human KMOE-2 cell growth in a cell viability assay, IC50=14.6178 μM
human EM-2 cell	Growth inhibition assay	Inhibition of human EM-2 cell growth in a cell viability assay, IC50=15.2841 μM
human RT-112 cell	Growth inhibition assay	Inhibition of human RT-112 cell growth in a cell viability assay, IC50=15.3984 μM
human DB cell	Growth inhibition assay	Inhibition of human DB cell growth in a cell viability assay, IC50=15.8513 μM
human NCI-H1770 cell	Growth inhibition assay	Inhibition of human NCI-H1770 cell growth in a cell viability assay
human CAL-54 cell	Growth inhibition assay	Inhibition of human CAL-54 cell growth in a cell viability assay, IC50=16.73 μM
human NB14 cell	Growth inhibition assay	Inhibition of human NB14 cell growth in a cell viability assay, IC50=17.6395 μM
human RPMI-7951 cell	Growth inhibition assay	Inhibition of human RPMI-7951 cell growth in a cell viability assay, IC50=19.1783 μM
human T47D cell	Growth inhibition assay	Inhibition of human T47D cell growth in a cell viability assay, IC50=21.2243 μM
human A549 cell	Growth inhibition assay	Inhibition of human A549 cell growth in a cell viability assay, IC50=21.2811 μM
human A2780 cell	Growth inhibition assay	Inhibition of human A2780 cell growth in a cell viability assay, IC50=21.8225 μM
human SK-MEL-24 cell	Growth inhibition assay	Inhibition of human SK-MEL-24 cell growth in a cell viability assay, IC50=33.0311 μM
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	404.3	Formule	C₁₉H₁₂F₄N₄O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	745833-23-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	C1=CC(=C(C(=C1)F)N(C2=NC(=C(C=C2)C(=O)N)C3=C(C=C(C=C3)F)F)C(=O)N)F

Oplosbaarheid

In vitro
Batch:

DMSO : 81 mg/mL (200.34 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

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%PEG300 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.	4.000mg/ml (9.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 80 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 formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met 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 de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

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

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

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. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	Highly selective, orally active inhibitor of p38 MAPK.
Targets/IC₅₀/Ki	p38α (Cell-free assay) 4 nM-20 nM
In vitro	Voorincubatie van bloedplaatjes met VX-702 (1 μM) remt de p38-activering (IC50 4 tot 20 nM) geïnduceerd door plaatjesagonisten waaronder trombine, SFLLRN, AYPGKF, U46619 en collageen, volledig of gedeeltelijk. Deze verbinding vertoont geen effect op de plaatjesaggregatie geïnduceerd door een van de p38 MAPK-agonisten in aanwezigheid of afwezigheid van antiplaatjestherapieën. Het remt de productie van IL-6, IL-1β en TNFα (IC50 = respectievelijk 59, 122 en 99 ng/mL) op een dosisafhankelijke manier.
In vivo	De halfwaardetijd van VX-702 is 16 tot 20 uur, met een mediane klaring van 3,75 L/u en een verdelingsvolume van 73 L/kg. Zowel AUC- als C_max-waarden zijn dosisproportioneel voor deze verbinding, die voornamelijk renaal wordt geklaard. Deze verbinding (in een dosis van 0,1 mg/kg tweemaal daags) heeft een gelijkwaardig effect. Bovendien deze chemische stof (5 mg/kg tweemaal daags), gemeten door het percentage remming van polsgewrichtserosie en ontstekingsscore. Het remt selectief de activering van p38 MAPK na ischemie zonder effecten op ERKs en JNKs. De MI/AAR-ratio is significant verlaagd in de 50 mg/kg-groep vergeleken met de 5 mg/kg- en voertuiggroepen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/15583748/ [2] http://eprints.utas.edu.au/3610/1/vx-702.pdf [3] http://eprints.utas.edu.au/3610/1/vx-702.pdf [4] http://circ.ahajournals.org/content/108/17.toc

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT00395577	Completed	Rheumatoid Arthritis	Vertex Pharmaceuticals Incorporated	November 2006	Phase 2

Technische ondersteuning

Gebruiksaanwijzing

Tel: +1-832-582-8158 Ext:3

Als u nog andere vragen heeft, laat dan een bericht achter.

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):