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
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL1289494;
ChemSpider	8087481;
IUPHAR/BPS	6058;
PubChem CID	9911830;
UNII	172030934T ;
CompTox Dashboard (EPA)	DTXSID20963865 ;
	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
Pharmacology
ATC code	L01XE34 (WHO)
	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.^[1] 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.^[2] It was developed by AVEO Pharmaceuticals.^[3] It is designed to inhibit all three VEGF receptors.^[4]

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.^[4]^[5] 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.^[5]

References

^ A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma, clinicaltrials.gov
^ Campas, C., Bolos, J., Castaner, R (2009). "Tivozanib". Drugs Fut. 34 (10): 793.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Aveo Kidney Cancer Drug Shows Success; Shares Up, By John Kell, Dow Jones Newswires^{[dead link]}
^ ^a ^b "Phase III Results Lead Aveo and Astellas to Plan Regulatory Submissions for Tivozanib". 3 Jan 2012.
^ ^a ^b "FDA Rejects Renal Cancer Drug Tivozanib". MedPage Today. June 30, 2013.

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[1] A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma, clinicaltrials.gov

[2] Campas, C., Bolos, J., Castaner, R (2009). "Tivozanib". Drugs Fut. 34 (10): 793.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[3] Aveo Kidney Cancer Drug Shows Success; Shares Up, By John Kell, Dow Jones Newswires^{[dead link]}

[Jan2012-4] "Phase III Results Lead Aveo and Astellas to Plan Regulatory Submissions for Tivozanib". 3 Jan 2012.

[FDArejects-5] "FDA Rejects Renal Cancer Drug Tivozanib". MedPage Today. June 30, 2013.

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