Accueil>>Signaling Pathways>> Tyrosine Kinase>> VEGFR>>Tivozanib (AV-951)

Tivozanib (AV-951)

Numéro de catalogue: GC12036

Le tivozanib (AV-951 ; KRN951) est un inhibiteur de la tyrosine kinase VEGFR puissant, sélectif et actif par voie orale avec une IC50 de 0,21, 0,16 et 0,24 nM pour VEGFR-1, VEGFR-2, VEGFR-3, respectivement. Le tivozanib inhibe l'angiogenèse et la perméabilité vasculaire dans les tissus tumoraux et présente une activité antitumorale. Le tivozanib a le potentiel pour la recherche sur le carcinome À cellules rénales métastatique (RCC) .

Tivozanib (AV-951) Structure chimique

Taille Prix Stock Qté
10mM (in 1mL DMSO)
64,00 $US
En stock
10mg
62,00 $US
En stock
25mg
88,00 $US
En stock
100mg
230,00 $US
En stock

Avis des clients

Basé sur les commentaires des clients.

Tél: (626) 353-8530 Email: sales@glpbio.com

Sample solution is provided at 25 µL, 10mM.

Product Documents

Contrôle de qualité & Fiche de Données de Sécurité

Afficher le lot actuel :

Protocol

Cell experiment [1]:

Cell lines

Human ovarian carcinoma cell lines, including A2780CP, OVCAR3 and SKOV3.

Preparation method

Soluble in DMSO >22.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10μm, 48h

Applications

Combination of tivozanib with the EGFR(Epidermal Growth Factor Receptor)-directed therapies displayed synergistic activity on cell growth inhibition and induction of apoptosis, suggesting that anti-VEGFR(vascular endothelial growth factor receptor) -targeted approaches induced sensitisation to the EGFR-directed therapies.

Clinical experiment [2]:

Diseases models

Patients with renal cell carcinoma(RCC)

Dosage form

1.5 mg OD for 3 weeks, oral administration

Application

Tivozanib exhibit an inhibitory profile with high sensitivity for inhibition of VEGFR family members. Patients receiving tivozanib had a PFS(Progression free survival) of 12.7 months – the best PFS reported in a phase III trial with mRCC.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Momeny M1, Sabourinejad Z2,3, et al, Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells. Sci Rep. 2017 Apr 6;7:45954. doi: 10.1038/srep45954.

[2]. Grünwald V1, Merseburger AS2. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come Eur J Cancer. 2013 Jul;49(11):2504-11. doi: 10.1016/j.ejca.2013.03.022. Epub 2013 Apr 16.

Arrière plan

Tivozanib is an inhibitor of tyrosine kinase with IC50 value of 160 pmol/L against VEGFR-2 [1].

Tivozanib is a quinoline-urea derivative. As a 2nd generation TKI, it has picomolar potency against VEGFR-1, -2 and -3, and minimal c-kit inhibition. Among this, Tivozanib has demonstrated a VEGFR-2 potency 2 orders of magnitude greater than sunitinib, sorafenib or pazopanib and a lower relative extent of off-target inhibition [1]. Tivozanib also shows to inhibit phosphorylation of the kinases PDGFRß and C-KIT at nanomolar level in cellular assays [2].

Tivozanib has shown antitumor activity in RCC xenograft models in addition to several other solid tumor models leading to its evaluation in clinical testing. The safety and efficacy of Tivozanib has been evaluated in several Phase I and Phase II trials. To compare the front-line use of tivozanib to sorafenib, a pivotal randomized Phase III trial has also been reported [3].

References:
[1] M.N. Fishman, S. Srinivas, R.J. Hauke, R.J. Amato, B. Esteves, M.M. Cotreau, A.L. Strahs, W.J. Slichenmyer, P. Bhargava, F.F. Kabbinavar. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. European Journal of Cancer. 2013(49):2841-2850.
[2] Viktor Grunwald, Axel Stuart Merseburger. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come? European Journal of Cancer. 2013(49):2504-2511.
[3] C Lance Cowey. Profile of tivozanib and its potential for the treatment of advanced renal cell carcinoma. Drug Design, Development and Therapy. 2013 (7): 519-527.

Propriétés chimiques

Cas No. 475108-18-0 SDF Non
Synonymes N/A
Chemical Name 1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea
Canonical SMILES CC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
Formula C22H19ClN4O5 M.Wt 454.86
Solubilité ≥ 22.75mg/mL in DMSO Storage Store at -20°C
Conseils généraux Afin d'obtenir une solubilité plus élevée, veuillez chauffer le tube à 37 °C et le secouer dans le bain à ultrasons pendant un certain temps. La solution mère peut être conservée à une température inférieure à -20 °C pendant plusieurs mois.
Condition d'expédition Solution d'échantillon d'évaluation : livré avec la glace bleue
Toute autre taille disponible : livré avec RT ou la glace bleue sur demande

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

  • Calculateur de molarité

  • Calculateur de dilution

Masse
=
Concentration
x
Volume
x
MW*
 
 
 
** Lors de la préparation de solutions mères, veillez à utiliser toujours le poids moléculaire spécifique au lot du produit indiqué sur l'étiquette du flacon et la Fiche de Données de Sécurité / Certificat d'Analyse (disponible en ligne).

Calculer

Avis

Review for Tivozanib (AV-951)

Average Rating: 5 ★★★★★ (Based on Reviews and 32 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for Tivozanib (AV-951)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.