Tivozanib (hydrate)

Tivozanib, also known as AV-951 and KRN-951, is an orally active, ATP-competitive, small-molecule, quinoline-urea derivative. Tivozanib is a pan-VEGFR tyrosine kinase inhibitor. In vitro: Tivozanib markedly inhibited the ligand-induced phosphorylation of VEGFR1\2 and 3 with the IC50 value of 30 nM\6.5 nM and 15 nM, respectively. Tivozanib also exihibited inhibitory effects on PDGFR and c-Ki with the IC50 value of 1.72 and 1.63 nmol/L, respectively. Tivozanib showed little activity against FGFR-1, Flt3, c-Met, EGFR and IGF-1R . Tivozanib blocked VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. It also inhibited VEGF-mediated migration of human umbilical vein endothelial cells . In vivo: In tumor xenografts athymic rat model, p.o. administration of tivozanib decreased the micro vessel density and suppressed VEGFR2 phosphorylation levels, especially at a concentration of 1mg/kg. Tivozanib almost completely inhibited tumor xenografts growth (TGI > 85%) in athymic rats. Tivozanib displayed antitumor activity against various human tumor xenografts, such as lung, breast, colon, pancreas, ovarian and prostate cancer.. In rat peritoneal disseminated tumor model, tivozanib prolonged the survival of the tumor-bearing rats with the MST of 53.5 days . Clinical trials: Tivozanib has entered phase III clinical trials in patients with advanced renal cell carcinoma. Tivozanib improved progression-free survival (PFS), but not overall survival (OS). The most common adverse events were hypertension and dysphonia . In patients with refractory, metastatic colorectal cancer, tivozanib has entered Multicenter phase II study .

Product information

CAS Number: 682745-40-0

Molecular Weight: 472.88

Formula: C22H21ClN4O6

Chemical Name: 1-{2-chloro-4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-3-(5-methyl-1,2-oxazol-3-yl)urea hydrate

Smiles: O.CC1=CC(NC(=O)NC2C=CC(=CC=2Cl)OC2=CC=NC3=CC(OC)=C(C=C32)OC)=NO1

InChiKey: VTWZGSZTIGEYIC-UHFFFAOYSA-N

InChi: InChI=1S/C22H19ClN4O5.H2O/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);1H2

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

Products are for research use only. Not for human use.