Tivozanib

Catalog No.S1207 Batch:S120703

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Technical Data

Formula

C22H19ClN4O5
Molecular Weight 454.86 CAS No. 475108-18-0
Solubility (25°C)* In vitro DMSO 20 mg/mL (43.96 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
2%DMSO 30%PEG300 68%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 1.000mg/ml (2.20mM) Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 680 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Tivozanib is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3.
Targets
VEGFR2 [1]
(Cell-free assay)		 VEGFR3 [1]
(Cell-free assay)		 EphB2 [1]
(Cell-free assay)		 VEGFR1 [1]
(Cell-free assay)		 PDGFRα [1]
(Cell-free assay)		 View More
6.5 nM 15 nM 24 nM 30 nM 40 nM
In vitro AV-951 is a novel quinoline-urea derivative. AV-951 blocks VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. [1]
In vivo In vivo studies show that AV-951 also decreases the micro vessel density and suppresses VEGFR2 phosphorylation levels in tumor xenografts, especially at a concentration of 1mg/kg (p.o. administration). AV-951 shows almost complete inhibition of tumor xenografts growth (TGI>85%) in athymic rats. [1] Another study in rat peritoneal disseminated tumor model shows that AV-951 could prolong the survival of the tumor-bearing rats with the MST of 53.5 days. AV-951 displays antitumor activity against many human tumor xenografts including lung, breast, colon, ovarian, pancreas and prostate cancer. [2]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase Assays

    Cell-free kinase assays are done in quadruplicate with 1 μM ATP to determine the IC50 values of AV-951 against a variety of recombinant receptor and nonreceptor tyrosine kinases including VEGFR1, VEGFR2, VEGFR3, c-Kit, PDGFRβ, Flt-3 and FGFR1.
Cell Assay:[1]
  • Cell lines

    Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts

  • Concentrations

    1 μM

  • Incubation Time

    15 minutes

  • Method

    Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts-based assays are done to determine the ability of AV-951 to inhibit ligand-dependent phosphorylation of tyrosine kinase receptors. The cells are starved overnight in appropriate basic medium containing 0.5% fetal bovine serum (FBS). The cells are incubated for 1 hour following the addition of AV-951 or 0.1% DMSO, and then stimulated with the cognate ligand at 37 °C. Receptor phosphorylation is induced for 5 minutes except for VEGFR3 (10 minutes), c-Met (10 minutes), and c-Kit (15 minutes). All the ligands used in the assays are human recombinant proteins, except for VEGF-C, a rat recombinant protein. Following cell lysis, receptors are immunoprecipitated with appropriate antibodies and subjected to immunoblotting with phosphotyrosine. Quantification of the blots and calculation of IC50 values are carried ou
Animal Study:[1]
  • Animal Models

    A549 xenografts in Athymic rats (RH-rnu/rnu)

  • Dosages

    1 mg/kg

  • Administration

    Oral administration

References

  • https://pubmed.ncbi.nlm.nih.gov/16982756/
  • https://pubmed.ncbi.nlm.nih.gov/18201272/

Customer Product Validation

On-chip angiogenesis assay. Fluorescence imaging of Tg(fli1a:EGFP) embryos at 64 hpf. Transgenic embryos were arrayed and immobilized at 16 hpf and continuously perfused with E3 media containing vehicle control (dimethyl sulfoxide) or selected small-molecule antiangiogenic drugs (Sunitinib and Tivozanib). Right panel: microscopic visualization of patterns of ISV. White arrows: normal ISV growth; blue arrows: partial ISV growth inhibition; and red arrows; complete ISV growth inhibition.

Data from [ Cytometry A , 2014 , 85(6), 537-47 ]

<p>After serum-starvation for 24 h, the MCF7 cells were co-treated with 10 nM TPA and the indicated doses VEGFR inhibitor, Tivozanib, for 24 h. The levels of fibronectin, p-PKC-α, p-ERK, p-AKT, t-AKT and β-actin protein expression were analyzed by western blotting. The levels of fibronectin mRNA were analyzed by real-time PCR. The results are representative of three independent experiments. The values shown are the means ±SEM. * P < 0.05, ** P < 0.01 vs. control. # P < 0.05, ## P < 0.01 vs. TPA-treated cells. Con: control. LY: LY294002, U: UO126, Go: Go6983, Akt IV: Akt IV inhibitor.</p>

Data from [ Cell Physiol Biochem , 2013 , 32(5), 1541-50 ]

<p> </p><p>Reversal effect of Tivozanib on the sensitivity of HEK/ABCB1 cells to vincrstine. The figure showes the survival curves of cells at different concentrations of vincristine with or without Tivozanib. Cell viability was determined by MTT Assay. HEK293 is human embryonic kidney cell line while HEK/ABCB1 is ABCB1-transfected cell line. Verapamil was used as a positive control of ABCB1 inhibitor.</p>

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<p> </p><p>Figure 7 shows the effect of Tivozanib on the accumulation of [<sup>3</sup>H]-mitoxantrone. The accumulation of [<sup>3</sup>H]-mitoxantrone in empty vector transfected HEK293/pcDNA3.1, ABCG2 vector transfected wild-type ABCG2-482-R2, mutant ABCG2-482-G2 and mutant ABCG2-482-T7 cells was measured by the Accumulation Assays. Columns are the mean of triplicate determinations; bars, SD. *P<0.05, **P<0.01 versus the control group. Fumitremorgin C (FTC) was used as a positive control of ABCG2 inhibitor.</p>

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Selleck's Tivozanib Has Been Cited by 45 Publications

APOE- ε4-induced Fibronectin at the blood-brain barrier is a conserved pathological mediator of disrupted astrocyte-endothelia interaction in Alzheimer's disease [ bioRxiv, 2025, 2025.01.24.634732] PubMed: 39975303
Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction [ Nat Commun, 2024, 15(1):4758] PubMed: 38902234
Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction [ Nat Commun, 2024, 15(1):4758] PubMed: 38902234
Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer [ Cell Rep Med, 2024, S2666-3791(24)00201-5] PubMed: 38670097
Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3 [ Biomed Pharmacother, 2024, 180:117533] PubMed: 39405909
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271
VEGF-A165a and angiopoietin-2 differently affect the barrier formed by retinal endothelial cells [ Exp Eye Res, 2024, 247:110062] PubMed: 39187056
ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma [ Cancer Res, 2023, 83(12):2034-2051] PubMed: 37078777
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma [ Biochem Pharmacol, 2023, 214:115681] PubMed: 37429423
Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7] PubMed: 35332332

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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