Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H19ClN4O5 |
Molecular Weight | 454.863 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C=C1OC)C(OC3=CC(Cl)=C(NC(=O)NC4=NOC(C)=C4)C=C3)=CC=N2
InChI
InChIKey=SPMVMDHWKHCIDT-UHFFFAOYSA-N
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)
Molecular Formula | C22H19ClN4O5 |
Molecular Weight | 454.863 |
Charge | 0 |
Count |
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Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24019545Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/23788831
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24019545
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/23788831
Tivozanib (formerly AV-951, KRN-951) is a potent and selective VEGFR tyrosine kinase inhibitor and inhibits angiogenesis and vascular permeability in tumor tissues. It completed phase III a trial investigation for the treatment of renal cell carcinomas, but has not been still approved. In addition, this drug is in the phase II of clinical trial for the investigation it in patients with glioblastoma and colorectal carcinoma.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2095227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=16982756 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Sample Use Guides
Advanced Renal Cell Carcinoma: 1.5 mg orally once daily. Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16982756
KRN951 (TIVOZANIB) potently inhibited VEGF-induced VEGFR-2 phosphorylation in endothelial cells at in vitro subnanomolar IC50 values (IC50 = 0.16 nmol/L). It also inhibited ligand-induced phosphorylation of platelet-derived growth factor receptor-beta (PDGFR-beta) and c-Kit (IC50 = 1.72 and 1.63 nmol/L, respectively). KRN951 blocked VEGF-dependent, but not VEGF-independent, activation of mitogen-activated protein kinases and proliferation of endothelial cells. In addition, it inhibited VEGF-mediated migration of human umbilical vein endothelial cells.
Substance Class |
Chemical
Created
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Sat Dec 16 15:46:52 GMT 2023
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Record UNII |
172030934T
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Record Status |
Validated (UNII)
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C93259
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Related Record | Type | Details | ||
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EXCRETED UNCHANGED |
FECAL
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
IC50
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BINDER->LIGAND |
Protein binding of tivozanib is ≥ 99%, primarily to albumin in vitro and is independent of
concentration.
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TARGET -> INHIBITOR |
IC50
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TARGET -> INHIBITOR |
IC50
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METABOLIC ENZYME -> SUBSTRATE |
expressed in extrahepatic tissues such as the lung and intestine, it is unlikely that this isoform
would be extensively involved in generating the metabolites observed following incubations
with human liver microsomes.
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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blood-to-plasma ratio | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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Females had a longer estimated T1/2 (129 hours) compared to males (110 hours). PHARMACOKINETIC |
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