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Tivozanib (AV-951)

Catalog No.
A2251
VEGFR inhibitor,potent and selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$94.00
In stock
10mg
$85.00
In stock
25mg
$120.00
In stock
100mg
$300.00
In stock

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt454.86
Cas No.475108-18-0
FormulaC22H19ClN4O5
Solubility≥22.75mg/mL in DMSO
Chemical Name1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea
SDFDownload SDF
Canonical SMILESCC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

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.

Biological Activity

Description Tivozanib is an inhibitor of tyrosine kinase with IC50 value of 160 pM for VEGFR-2.
Targets VEGFR-2          
IC50 160 pM          

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