Tivozanib

Tivozanib

Names
IUPAC name 1-{2-Chloro-4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-3-(5-methylisoxazol-3-yl)urea
Other names AV-951
Identifiers
ChEMBL	ChEMBL1289494
ChemSpider	8087481
IUPHAR/BPS	6058
Jmol 3D model	Interactive image
PubChem	9911830
UNII	172030934T Y
InChI InChI=1S/C22H19ClN4O5/c1-12-8-21(27-32-12)26-22(28)25-16-5-4-13(9-15(16)23)31-18-6-7-24-17-11-20(30-3)19(29-2)10-14(17)18/h4-11H,1-3H3,(H2,25,26,27,28)
SMILES O=C(Nc1noc(c1)C)Nc4ccc(Oc2c3cc(OC)c(OC)cc3ncc2)cc4Cl
Properties
Chemical formula	C22H19ClN4O5
Molar mass	454.87 g·mol−1
Vapor pressure	{{{value}}}
Pharmacology
ATC code	L01XE34
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Tivozanib (AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It completed a trial investigation for the treatment of renal cell carcinomas. The results did not result in FDA approval.

Mechanism

An oral quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor. It was developed by AVEO Pharmaceuticals. It is designed to inhibit all three VEGF receptors.

Results

Phase III results on advanced renal cell carcinoma suggested a 30% or 3 months improvement in median PFS compared to sorafenib but showed an inferior overall survival rate of the experimental arm versus the control arm. The Food and Drug Administration's Oncologic Drugs Advisory Committee voted in May 2013 13 to 1 against recommending approval of tivozanib for renal cell carcinoma. The committee felt the drug failed to show a favorable risk-benefit ratio and questioned the equipose of the trial design, which allowed control arm patients who used sorafenib to transition to tivozanib following progression disease but not those on the experimental arm using tivozanib to transition to sorafenib. The application was formally rejected by the FDA in June 2013, saying that approval would require additional clinical studies.