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Combretastatin A4 Microtubule Associated remmer

Name: Combretastatin A4
Brand: Selleck Chemicals
SKU: S7783
Rating: 5 (7 reviews)

Cat.Nr.S7783

Combretastatin A4 is een microtubule-targetend middel dat β-tubuline bindt met K_d van 0,4 μM. Fase 3.

Combretastatin A4 Microtubule Associated remmer Chemical Structure

Chemische structuur

Moleculair gewicht: 316.35

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Kwaliteitscontrole

Batch: S778301 DMSO]63 mg/mL]false]Ethanol]34 mg/mL]false]Water]Insoluble]false Zuiverheid: 99.87%

Genoemd in Nature Medicine voor zijn topkwaliteit
COA
NMR
SDS
Datasheet

99.87

Gerelateerde doelwitten	Akt Wnt/beta-catenin PKC HSP ROCK Integrin Bcr-Abl Actin FAK Kinesin
Overige Microtubule Associated Inhibitoren	Nocodazole MMAF Patupilone (Epothilone B) Lexibulin (CYT997) CW069 Epothilone A ABT-751 (E7010) TAI-1 Cucurbitacin B INH1

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving
SKMEL-5	Growth inhibition assay		Cytotoxic concentration required to inhibit 50% cell growth in SKMEL-5 melanoma cell lines, ED50=3.00E-08 μM
A-549	Growth inhibition assay		Cytotoxic concentration required to inhibit 50% cell growth in A-549 lung carcinoma cell lines, ED50=1.20E-06 μM
MCF-7	Growth inhibition assay		Cytotoxic concentration required to inhibit 50% cell growth in MCF-7 breast carcinoma cell lines, ED50=3.80E-06 μM
HT-29	Growth inhibition assay		Cytotoxic concentration required to inhibit 50% cell growth in HT-29 colon adenocarcinoma cell lines, ED50=1.20E-06 μM
MLM melanoma cell	Growth inhibition assay		Cytotoxic concentration required to inhibit 50% cell growth in MLM melanoma cell lines, ED50=1.40E-06 μM
M14	Cytotoxicity assay		In vitro cytotoxic activity was tested against human melanoma cancer (M14) cell line, GI50=0.0001 μM
SK-OV3	Cytotoxicity assay		In vitro cytotoxic activity tested against human ovarian cancer (SK-OV3) cell line, GI50=0.0001 μM
HL60 cells	Cytotoxicity assay	72 h	Cytotoxicity against human HL60 cells after 72 hrs by MTT assay, IC50=0.0001 μM
SK-OV-3	Growth inhibition assay	48 h	Growth inhibition of human SK-OV-3 after 48 hrs by SRB assay, GI50=0.00013 μM
HepG2 cells	Cytotoxicity assay		Cytotoxicity against human HepG2 cells, IC50=0.00014 μM
ZR-75-1	Cytotoxicity assay		Cytotoxicity against ZR-75-1 cell line, IC50=0.00024 μM
HeLa cell	Cytotoxicity assay		Cytotoxicity against HeLa cell line, IC50=0.0003 μM
HCT116 cell	Cytotoxicity assay		Cytotoxicity against HCT116 cell line, IC50=0.00035 μM
KBV1 cells	Cytotoxicity assay	72 h	Cytotoxicity against human vinblastine-resistant KBV1 cells after 72 hrs by MTT assay, IC50=0.0004 μM
SKOV3	Cytotoxicity assay		Cytotoxicity against human SKOV3 cells by SRB assay, GI50=0.00042 μM
SKOV3 cells	Growth inhibition assay		Growth inhibition of human SKOV3 cells by sulforhodamine B assay, GI50=0.00042 μM
HeLa cells	Cytotoxicity assay		Cytotoxicity against human HeLa cells by MTT assay, IC50=0.00051 μM
DU145 cells	Cytotoxicity assay		Cytotoxicity against human DU145 cells by SRB assay, GI50=0.00054 μM
DU145 cells	Growth inhibition assay		Growth inhibition of human DU145 cells by sulforhodamine B assay, GI50=0.00054 μM
SK-N-BE	Proliferation assay	72 h	Antiproliferative activity in human SK-N-BE cells assessed as cell viability after 72 hrs by MTT assay, IC50=0.00058 μM
NCIH460 cells	Cytotoxicity assay	48 h	Cytotoxicity against human NCIH460 cells after 48 hrs by SRB assay, GI50=0.0006 μM
KB-VIN10 cells	Proliferation assay	72 h	Antiproliferative activity against human KB-VIN10 cells over-expressing P-gp 170/MDR1 after 72 hrs by methylene blue assay, IC50=0.0007 μM
HCT116 cells	Cytotoxicity assay	72 h	Cytotoxicity against human HCT116 cells assessed as reduction of [3H]thymidine incorporation after 72 hrs by scintillation counting, IC50=0.00074 μM
DU145 cells	Cytotoxicity assay	48 h	Cytotoxicity against human DU145 cells after 48 hrs by SRB assay, GI50=0.0008 μM
RS4:11 cells	Proliferation assay	72 h	Antiproliferative activity against human RS4:11 cells after 72 hrs by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, IC50=0.0008 μM
HCT 116	Growth inhibition assay		Concentration which produces 50% inhibition of growth of human colon tumor HCT 116, IC50=0.0009 μM
HeLa cells	Cytotoxicity assay	72 h	Cytotoxicity against human HeLa cells after 72 hrs by resazurin based fluorescence assay, IC50=0.0009 μM
BNL 1ME A.7R.1 cells	Cytotoxicity assay		Cytotoxicity against mouse BNL 1ME A.7R.1 cells, IC50=0.0009 μM
Calu6	Proliferation assay	48 h	Antiproliferative activity against human Calu6 after 48 hrs by spectrophotometry, IC50=0.00094 μM
melanoma B16 cell	Growth inhibition assay		Concentration which produces 50% inhibition of growth of murine melanoma B16 cell line, IC50=0.001 μM
DU145 cells	Cytotoxicity assay		Cytotoxicity against human DU145 cells by SRB assay, GI50=0.001 μM
HCT116 cells	Proliferation assay	72 h	Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay, IC50=0.001 μM
HCT15 cells	Proliferation assay	72 h	Antiproliferative activity against human HCT15 cells after 72 hrs by MTS assay, IC50=0.001 μM
HL60 cells	Proliferation assay	72 h	Antiproliferative activity against human HL60 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.001 μM
A10 cells	Growth inhibition assay	48 h	Growth inhibition of rat A10 cells after 48 hrs by MTT assay, IC50=0.001 μM
HUVEC cells	Growth inhibition assay	48 h	Growth inhibition of HUVEC cells after 48 hrs by MTT assay, IC50=0.001 μM
HL60 cells	Cytotoxicity assay	72 h	Cytotoxicity against human HL60 cells after 72 hrs by MTT assay, IC50=0.001 μM
HL60 cells	Proliferation assay	72 h	Antiproliferative activity against human HL60 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50=0.001 μM
NCI-H522 cells	Growth inhibition assay	48 h	Growth inhibition of human NCI-H522 cells after 48 hrs by SRB assay, GI50=0.001 μM
MDA-MB-435 cells	Growth inhibition assay	48 h	Growth inhibition of human MDA-MB-435 cells after 48 hrs by SRB assay, GI50=0.001 μM
OVCAR3	Growth inhibition assay	48 h	Growth inhibition of human OVCAR3 cells after 48 hrs by SRB assay, GI50=0.001 μM
NCI/ADR-RES cells	Growth inhibition assay	48 h	Growth inhibition of human NCI/ADR-RES cells after 48 hrs by SRB assay, GI50=0.001 μM
PC3 cells	Growth inhibition assay	48 h	Growth inhibition of human PC3 cells after 48 hrs by SRB assay, GI50=0.001 μM
DU145 cells	Growth inhibition assay	48 h	Growth inhibition of human DU145 cells after 48 hrs by SRB assay, GI50=0.001 μM
MDA-MB-231 cells	Growth inhibition assay	48 h	Growth inhibition of human MDA-MB-231 cells after 48 hrs by SRB assay, GI50=0.001 μM
CEM cells	Cytotoxicity assay	72 h	Cytotoxicity against human CEM cells after 72 hrs by MTT assay, IC50=0.001 μM
HCT116 cells	Cytotoxicity assay	72 h	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50=0.001 μM
MDA-MB-435 cells	Cytotoxicity assay	72 h	Cytotoxicity against human MDA-MB-435 cells after 72 hrs by MTT assay, IC50=0.001 μM
HaCaT cells	Proliferation assay		Antiproliferative activity against human HaCaT cells assessed as cell viability by MTT assay, IC50=0.001 μM
HL60 cells	Proliferation assay	72 h	Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay, IC50=0.001 μM
HL60 cells	Proliferation assay	72 h	Antiproliferative activity against human HL60 cells after 72 hrs by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, IC50=0.001 μM
HT-29	Growth inhibition assay		Growth inhibition of human HT-29 cells by MTT assay, IC50=0.001 μM
HL60 cells	Proliferation assay	72 h	Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay, IC50=0.001 μM
Hs578T cells	Growth inhibition assay	48 h	Growth inhibition of human Hs578T cells after 48 hrs by SRB assay, GI50=0.001 μM
HL60 cells	Cytotoxicity assay	72 h	Cytotoxicity against human HL60 cells after 72 hrs by MTT assay, IC50=0.001 μM
SKOV3 cells	Growth inhibition assay		Growth inhibition of human SKOV3 cells by MTT assay, IC50=0.001 μM
MDA-MB-468 cells	Cytotoxicity assay	4 days	Cytotoxicity against human MDA-MB-468 cells assessed as cell viability after 4 days by MTS assay, IC50=0.0011 μM
MCF7 cells	Proliferation assay	72 h	Antiproliferative activity in human MCF7 cells assessed as cell viability after 72 hrs by MTT assay, IC50=0.00111 μM
H460	Cytotoxicity assay		Cytotoxicity against human H460 cells by sulforhodamine B test, IC50=0.0012 μM
H460	Proliferation assay		Antiproliferative activity against human H460 cells, IC50=0.00124 μM
NCI-H460 cells	Cytotoxicity assay	72 h	Cytotoxic activity against human NCI-H460 cells after 72 hrs by sulforhodamine B test, IC50=0.0013 μM
OVCAR8 cells	Growth inhibition assay	96 h	Growth inhibition of human OVCAR8 cells overexpressing P-glycoprotein after 96 hrs, IC50=0.0013 μM
NCI/ADR-RES cells	Cytotoxicity assay		Cytotoxicity against human NCI/ADR-RES cells assessed as growth inhibition by trypan blue exclusion assay, IC50=0.0013 μM
OVCAR8 cells	Cytotoxicity assay	96 h	Cytotoxicity against human OVCAR8 cells assessed as growth inhibition after 96 hrs by Giemsa staining-based light microscopy, IC50=0.0013 μM
NCI/ADR-RES cells	Cytotoxicity assay	96 h	Cytotoxicity against human NCI/ADR-RES cells assessed as growth inhibition after 96 hrs by Giemsa staining-based light microscopy, IC50=0.0013 μM
OVCAR8 cells	Cytotoxicity assay		Cytotoxicity against human OVCAR8 cells assessed as growth inhibition by trypan blue exclusion assay, IC50=0.0013 μM
HuTu 80 cells	Proliferation assay	72 h	Antiproliferative activity in human HuTu 80 cells assessed as cell viability after 72 hrs by MTT assay, IC50=0.00137 μM
K562 cells	Cytotoxicity assay		Cytotoxicity against human K562 cells, IC50=0.0014 μM
NCI/ADR (MDR) cells	Function assay		Cell cycle arrest in NCI/ADR (MDR) cells by accumulation at G2/M phase, IC50=0.0015 μM
HUVEC	Proliferation assay		Antiproliferative activity against human HUVEC, IC50=0.0015 μM
KB cell	Proliferation assay		Antiproliferative activity against human KB cell line by methylene blue dye assay, IC50=0.0015 μM
KB-VIN10 cell	Proliferation assay		Antiproliferative activity against human KB-VIN10 cell line by methylene blue dye assay, IC50=0.0015 μM
Human SH-SY5Y neuroblastoma cells	Function assay		Inhibitory concentration against Human SH-SY5Y neuroblastoma cells, IC50=0.0015 μM
SW620 cells	Proliferation assay	72 h	Antiproliferative activity in human SW620 cells assessed as cell viability after 72 hrs by MTT assay, IC50=0.00152 μM
Molt4/C8 cells	Proliferation assay		Antiproliferative activity against human Molt4/C8 cells, IC50=0.0016 μM
ACHN cell	Proliferation assay		Antiproliferative activity against drug resistant ACHN cell line expressing MDR1 by Alamar Blue assay, IC50=0.0016 μM
Molt4/C8 cells	Proliferation assay	3 days	Antiproliferative effect against human Molt4/C8 cells after 3 days, IC50=0.0016 μM
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	316.35	Formule	C₁₈H₂₀O₅	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	117048-59-6	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)O

Oplosbaarheid

In vitro
Batch:

DMSO : 63 mg/mL (199.14 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 34 mg/mL

Water : 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.

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

Targets/IC₅₀/Ki	β-tubulin 0.4 μM(Kd)
In vitro	Combretastatin A4 remt de groei van MDA-MB-231, A549, Hela, HL-60, SF295, HCT-8, MDA-MB435, PC3M, OVCAR-8, NCI-H358M en lymfocytcellen met IC50 van respectievelijk 2,8, 3,8, 0,9, 2,1, 6,2, 5,3, 7,9, 4,7, 0,37, 8 en 3,2 nM. 1 μM van deze verbinding remt de tubulinepolymerisatie met 35%, en 10 μM blokkeert de tubulinepolymerisatie bijna volledig. Dit chemische middel vertoont een grote relatieve bindingscapaciteit, die 78% van de colchicinebinding bereikt.
Kinase Assay	Competitieve bindingstest met LC-MS/MS
Kinase Assay	Colchicine (1,2 μM) wordt geïncubeerd met tubuline (1,3 mg/mL) in de incubatiebuffer (80 mM PIPES, 2,0 mM MgCl2, 0,5 mM EGTA, pH 6,9) bij 37℃ gedurende 1 uur. Variërende concentraties (0,1 − 125 μM) van deze verbinding worden gebruikt om te concurreren met colchicine dat oorspronkelijk aan tubuline gebonden was. Na incubatie wordt het filtraat verkregen. Het vermogen van het analogon om de binding van colchicine te remmen, wordt uitgedrukt als een percentage van de controlebinding in afwezigheid van enige concurrent.
In vivo	In het NT2- en MDA-MB-231-mammacarcinoommodel induceert toediening van Combretastatin A4 (100 mg/kg, i.p.) een significante afname van lipiden R1 en een vermindering van tumor pO2 gemeten door elektronparamagnetische resonantie (EPR) oximetrie. Deze verbinding (100 mg/kg, i.p.) vermindert significant de K^trans bij mannelijke NMRI-muizen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/24669888/ [2] https://pubmed.ncbi.nlm.nih.gov/25765253/ [3] https://pubmed.ncbi.nlm.nih.gov/25323069/

Technische ondersteuning

Gebruiksaanwijzing

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

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Veelgestelde vragen

Vraag 1:
How to make solution for in vivo IP injection of it?

Antwoord:
We've tested some vehicles for this compound, and found it can be dissolved in 5% DMSO+50% PEG 300+ddH2O at 30mg/ml clearly. When prepare the solution, please dissolve it in DMSO clearly first. Then add PEG, after they mixed well, then dilute with water.

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