Research Area
Product Type
United States ( Change Country )
Tivozanib (AV-951) Chemical Structure
Linifanib (ABT-869)
Linifanib (ABT869) is a structurally novel, potent RTK and VEGF and PDGF receptor families inhibitor for, PDGFR-β, KDR, and CSF-1R, with IC50 of 0.2 nM, 2 nM, 4 nM, and 7 nM, respectively.
Axitinib
Axitinib (AG-013736) is a multiple receptor kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-β and c-KIT with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
BIBF1120 (Vargatef)
BIBF1120 (Vargatef) is a potent VEGF receptor (VEGFR), PDGFR and FGFR kinase inhibitor for VEGFR1, VEGFR2, VEGFR3 with IC50 of 34 nM, 5 nM and 5 nM, respectively.
Cediranib (AZD2171)
Cediranib (AZD2171) is a highly potent VEGFR2 inhibitor for VEGF-stimulated proliferation and KDR phosphorylation with IC50 of 0.4 nM and 0.5 nM, respectively.
Dovitinib (TKI-258)
Dovitinib(TKI-258) is a highly potent, novel multitargeted growth factor receptor kinase inhibitor with IC50 of 1, 2, 5, 10, 8, 27, 36 nM for FLT3, c-KIT, FGFR, VEGFR1/2/3, PDGFRß and CSF-1R, respectively.
Dasatinib (BMS-354825)
Dasatinib also known as BMS-354825, Sprycel, BMS354825 is ATP-competitive, dual SRC/ABL inhibitor. BMS-354825 inhibits all members of the Src family, including c-Src, Lck, Fyn, and Yes (IC50 < 1.1nmol/L).
Imatinib Mesylate
Imatinib Mesylate is a multitargeted c-kit, PDGF-R and c-ABL inhibitor with IC50 of 3.9 and 2.9 μM for the inhibition of T-cell proliferation stimulated by DCs and PHA, respectively.
Motesanib Diphosphate (AMG-706)
Motesanib (AMG-706) is a multiple inhibitor of VEGFR1/2/3(IC50: 2 ηM /3 ηM /6 ηM),PDGFR (84ηM), kit (8ηM), and Ret (59ηM)receptors
Pazopanib HCl
Pazopanib HCl is a VEGFR inhibitor, IC50 of 10, 30 and 47 nM for VEGFR-1, -2, and -3.
Sorafenib (Nexavar)
Sorafenib (Nexavar) is a novel, small molecular inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and RAF/MEK/ERK cascade inhibitor with an IC50 of 6, 22, 38 nM for Raf-1, wt BRAF and V599E mutant BRAF.
Biological Activity
| Information | AV-951 (Tivozanib, KRN-951) is a potent and selective VEGFR inhibitor to all three VEGF receptors, VEGFR-1, -2 and -3 with IC50 of 0.21 nM, 0.16 nM and 0.24 nM, respectively. | |||||
|---|---|---|---|---|---|---|
| Targets | VEGFR-1 | VEGFR-2 | VEGFR-3 | |||
| IC50 | 0.21 nM [1] | 0.16 nM [1] | 0.24 nM [1] | |||
| In vitro | AV-951 is a novel quinoline-urea derivative. AV-951 inhibits phosphorylation of PDGFRß and c-Kit with IC50 of 1.72 and 1.63 nM, respectively. 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 VEGFR-2 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] | |||||
| Clinical Trials | AV-951 is currently in Phase II clinical trial in treatment of gastrointestinal cancer. | |||||
| Features | ||||||
Protocol
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 VEGFR-1, VEGFR-2, VEGFR-3, c-Kit, PDGFR-β, 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 ℃. Receptor phosphorylation was induced for 5 minutes except for VEGFR-3 (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 out. |
Animal Study:[1]
| Animal Models: | A549 xenografts in Athymic rats (RH-rnu/rnu) |
|---|---|
| Formulation: | 0.5% methylcellulose in distilled water |
| Dosages: | 1 mg/kg |
| Administration: | Oral administration |
Product Information
| Molecular Weight (WM): | 454.86 |
|---|---|
| Formula: | C22H19ClN4O5 |
| CAS No.: | 475108-18-0 |
| Synonyms: |
N/A
|
| Dissolve in (25°C): | DMSO ≥39mg/mL |
| Water <1mg/mL | |
| Ethanol <1mg/mL | |
| Storage: | 2 years-20°CPowder |
| 1 week-4°Cin DMSO | |
| 1 month-80°in DMSO |
Quality Control & MSDS
Research Area
Notes:
Related Inhibitors
Recommended Screening Libraries
Chemical Library
A collection of 864 bioactive compounds
Inhibitor Library
A collection of 481 inhibitors
Kinase Inhibitor Library
A collection of 194 kinase inhibitors
Tyrosine Kinase Inhibitor Library
A collection of 85 tyrosine kinase inhibitors.
FDA Approved Drug Library
A collection of 426 FDA approved drugs
Natural Product Library
A collection of 139 natural products
Chemotherapeutic Agent Library
A collection of 40 chemotherapeutic agents
Epigenetics Compound library
A unique collection of 17 small molecule modulators
Stem Cell Compound library
A unique collection of 47 small molecule inhibitors
GPCR Compound library
A unique collection of 63 GPCR small molecules
Recently Viewed Items
Keywords:buy Tivozanib (AV-951) | Tivozanib (AV-951) supplier | purchase Tivozanib (AV-951) | Tivozanib (AV-951) cost | Tivozanib (AV-951) manufacturer | order Tivozanib (AV-951) | Tivozanib (AV-951) distributor