Identification
- Summary
Tivozanib is a kinase inhibitor to treat adult patients with renal cell carcinoma (RCC) who have failed prior systemic therapies or experienced relapsed disease.
- Brand Names
- Fotivda
- Generic Name
- Tivozanib
- DrugBank Accession Number
- DB11800
- Background
Renal cell carcinoma (RCC) is responsible for 3% of cancer cases2 and is one of the 10 most common cancers in adults. The average age of diagnosis is between age 65 to 74.10 Tivozanib, also known as FOTIVDA, is a kinase inhibitor developed to treat adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) after prior failed systemic therapies. It was approved on March 10, 2021 by the FDA. Marketed by Aveo Oncology, tivozanib is a promising therapy for individuals with RCC who have not been treated successfully with other therapies.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Tivozanib (DB11800)
- Weight
- Average: 454.863
Monoisotopic: 454.104397445 - Chemical Formula
- C22H19ClN4O5
- Synonyms
- Tivozanib
- External IDs
- AV 951
- AV-951
- AV951
- KIL-8951
- KRN 951
- KRN-951
Pharmacology
- Indication
Tivozanib is approved in the USA for the treatment of relapsed or refractory renal cell carcinoma in adult patients who have undergone two or more systemic therapies.9 In the UK and other countries, is indicated as first line therapy of adults with advanced renal cell carcinoma (RCC) and VEGFR and mTOR pathway inhibitor-naïve patients after disease progression following one previous treatment with cytokine therapy for advanced disease.8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Advanced renal cell carcinoma •••••••••••• ••••• ••••• •••••••••••••••• ••••••• ••••••••••• ••••• ••••• •••••••• •••••••• •••• ••••••••••••••• Treatment of Advanced renal cell carcinoma •••••••••••• ••••• Treatment of Renal cell adenocarcinoma •••••••••••• ••••• ••••••• Treatment of Renal cell adenocarcinoma •••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Tivozanib inhibits growth factor receptors, treating renal cell carcinoma. In mice and rats, tivozanib inhibits tumour angiogenesis, tumour growth, and vascular permeability.9 Tivozanib was shown to frequently cause hypertension in clinical trials; hypertension must be managed before initiating therapy. Cardiac QT segment prolongation was reported in a tivozanib cardiac safety study, however the reactions were not considered clinically serious.8 In clinical studies, levels of serum soluble VEGFR2 (sVEGFR2) decreased with time and this effect increased with tivozanib exposure, and sVEGFR2 may serve as a pharmacodynamic marker of VEGFR inhibition.13
- Mechanism of action
The VHL mutation-HIF upregulation-VEGF transcription is the main pathway implicated in the growth of renal cell carcinoma. Vascular endothelial growth factor receptors (VEGFR receptors) are important targets for tyrosine kinase inhibitors, which halt the growth of tumours.7 Tivozanib is a tyrosine kinase inhibitor that exerts its actions by inhibiting the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3 and inhibits other kinases such as c-kit and platelet derived growth factor beta (PDGFR β). The above actions inhibit tumour growth and progression, treating renal cell carcinoma.7,9
Target Actions Organism AVascular endothelial growth factor receptor 1 inhibitorHumans AVascular endothelial growth factor receptor 2 inhibitorHumans AVascular endothelial growth factor receptor 3 inhibitorHumans AMast/stem cell growth factor receptor Kit inhibitorHumans APlatelet-derived growth factor receptor beta inhibitorHumans UReceptor-type tyrosine-protein kinase FLT3 inhibitorHumans UPlatelet-derived growth factor receptor alpha inhibitorHumans UProtein-tyrosine kinase 6 Not Available Humans UAngiopoietin-1 receptor Not Available Humans UFibroblast growth factor receptor 1 inhibitorHumans UHepatocyte growth factor receptor inhibitorHumans - Absorption
The median Tmax of tivozanib is 10 hours, however, can range from 3 to 24 hours.9 A pharmacokinetic study in 8 healthy subjects revealed a Cmax and AUC for radiolabeled tivozanib of 12.1 ± 5.67 ng/mL and 1084 ± 417.0 ng·h/mL, respectively.3 Steady-state tivozanib concentrations are achieved at concentrations 6-7 times higher the normal dose.13
- Volume of distribution
Tivozanib has an apparent volume of distribution (V/F) of 123 L.9
- Protein binding
In vitro, the protein binding of tivozanib is mainly bound to albumin at a rate of ≥ 99%.9
- Metabolism
Tivozanib is primarily metabolized by CYP3A4.4,8 After oral ingestion of a radiolabeled 1.34 mg dose of tivozanib in healthy volunteers, unchanged tivozanib accounted for 90% of the radioactive drug detected in serum.9
- Route of elimination
Tivozanib is primarily excreted in the feces. After oral ingestion of a radiolabeled 1.34 mg dose of tivozanib in healthy volunteers, 79% of the administered dose was found in the feces (with 26% unchanged) and 12% was found in the urine solely as metabolites.3,9
- Half-life
The half-life of tivozanib is about 111 hours according to prescribing information.9 Information from clinical studies reveals a half-life of 4-5 days.3,13
- Clearance
The apparent clearance (CL/F) of tivozanib is approximately 0.75 L/h.9
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
LD50 information for tivozanib is not readily available in the literature, however the European Medicines Agency (EMA) assessment report indicates the oral maximum tolerated dose (MTD) in mice was 524 mg/kg; doses ≥ 750 mg/kg led to severe and lethal effects. In rats, the oral MTD was to 276 mg/kg; at doses ≥ 369 mg/kg, severe effects and death occurred.12
In tivozanib monotherapy studies, two patients received overdoses of tivozanib. One volunteer with a prior history of hypertension experienced aggravated uncontrolled hypertension that resulted in death after taking 3 doses of 1340 microgram tivozanib in one day (total of 4020 micrograms). A second patient patient ingested two doses of 1340 microgram tivozanib in one day (total of 2680 micrograms), and experienced no adverse effects. Carefully control blood pressure before starting tivozanib; regularly monitor blood pressure during treatment. In the case of a confirmed or suspected overdose, discontinue tivozanib, monitor the patient closely, and provide supportive treatment as necessary. No antidote exists for an overdose with tivozanib.8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Tivozanib may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abrocitinib The serum concentration of Tivozanib can be increased when it is combined with Abrocitinib. Acetaminophen The metabolism of Tivozanib can be increased when combined with Acetaminophen. Adagrasib The serum concentration of Tivozanib can be increased when it is combined with Adagrasib. Afatinib Tivozanib may decrease the excretion rate of Afatinib which could result in a higher serum level. - Food Interactions
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Tivozanib hydrochloride 8A9H4VK35Z 682745-41-1 RQXMKRRBJITKRN-UHFFFAOYSA-N - International/Other Brands
- Fotivda (AVEO Oncology)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fotivda Capsule 1.34 mg/1 Oral Aveo Pharmaceuticals, Inc. 2021-03-10 Not applicable US 
Fotivda Capsule 0.89 mg/1 Oral Aveo Pharmaceuticals, Inc. 2021-03-10 Not applicable US Fotivda Capsule 890 ?g Oral Recordati Netherlands B.V. 2020-12-16 Not applicable EU 
Fotivda Capsule 1340 ?g Oral Recordati Netherlands B.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- L01EK03 — Tivozanib
- Drug Categories
- Amides
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Benzene Derivatives
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- P-glycoprotein substrates
- Protein Kinase Inhibitors
- Receptors, Vascular Endothelial Growth Factor, antagonists & inhibitors
- Tyrosine Kinase Inhibitors
- Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Ethers
- Direct Parent
- Diarylethers
- Alternative Parents
- Quinolines and derivatives / N-phenylureas / Anisoles / Phenoxy compounds / Alkyl aryl ethers / Chlorobenzenes / Pyridines and derivatives / Imidolactams / Aryl chlorides / Isoxazoles show 10 more
- Substituents
- Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid / Carbonic acid derivative / Carbonyl group show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 172030934T
- CAS number
- 475108-18-0
- InChI Key
- SPMVMDHWKHCIDT-UHFFFAOYSA-N
- 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)
- IUPAC Name
- 1-{2-chloro-4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-3-(5-methyl-1,2-oxazol-3-yl)urea
- SMILES
- COC1=C(OC)C=C2C(OC3=CC(Cl)=C(NC(=O)NC4=NOC(C)=C4)C=C3)=CC=NC2=C1
References
- Synthesis Reference
Liu, M. X., Hu, L. X., Wang, X. W., & Zhu, H. D. (2011). Synthesis of Anti-Cancer Targeted Therapies Drug Tivozanib. Advanced Materials Research, 396–398, 1490–1492. https://doi.org/10.4028/www.scientific.net/amr.396-398.1490
- General References
- Cairns P: Renal cell carcinoma. Cancer Biomark. 2010;9(1-6):461-73. doi: 10.3233/CBM-2011-0176. [Article]
- Pallagani L, Choudhary GR, Himanshu P, Madduri VKS, Singh M, Gupta P, Shrivastava N, Baid G, Meenakshi R, Aasma N, Pareek P, Sanjeev M: Epidemiology and Clinicopathological Profile of Renal Cell Carcinoma: A Review from Tertiary Care Referral Centre. J Kidney Cancer VHL. 2021 Jan 20;8(1):1-6. doi: 10.15586/jkcvhl.2021.154. eCollection 2021. [Article]
- Cotreau MM, Hale CL, Jacobson L, Oelke CS, Strahs AL, Kochan RG, Sanga M, Slichenmyer W, Vargo DL: Absorption, Metabolism, and Excretion of [(14) C]-Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open-Label, Mass-Balance Study. Clin Pharmacol Drug Dev. 2012 Jul;1(3):102-9. doi: 10.1177/2160763X12447303. [Article]
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- Cotreau MM, Massmanian L, Strahs AL, Slichenmyer W, Vargo DL: The effect of food on the pharmacokinetics of tivozanib hydrochloride. Clin Pharmacol Drug Dev. 2014 Mar;3(2):158-62. doi: 10.1002/cpdd.76. Epub 2013 Oct 30. [Article]
- Kim ES: Tivozanib: First Global Approval. Drugs. 2017 Nov;77(17):1917-1923. doi: 10.1007/s40265-017-0825-y. [Article]
- Jacob A, Shook J, Hutson TE: Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma. Future Oncol. 2020 Oct;16(28):2147-2164. doi: 10.2217/fon-2020-0443. Epub 2020 Jul 21. [Article]
- EMC Summary of Product Characteristics: Fotivda (tivozanib hydrochloride monohydrate) oral capsules [Link]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- Cancer.org: Key Statistics About Kidney Cancer [Link]
- Cayman Chem safety data sheet: Tivozanib hydrate [Link]
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
- AVEO Oncology: Tivozanib hydrochloride pharmacokinetic/pharmacodynamic analysis of blood pressure and soluble vascular endothelial growth factor receptor 2 (sVEGFR2) in patients with advanced renal cell carcinoma [Link]
- External Links
- PubChem Compound
- 9911830
- PubChem Substance
- 347828149
- ChemSpider
- 8087481
- BindingDB
- 50331095
- 2534233
- ChEBI
- 91327
- ChEMBL
- CHEMBL1289494
- ZINC
- ZINC000001489430
- PDBe Ligand
- AV9
- Wikipedia
- Tivozanib
- PDB Entries
- 4ase / 8bem
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Renal Cell Carcinoma (RCC) 1 3 Completed Treatment Advanced Renal Cell Carcinoma 2 3 Completed Treatment Renal Cell Carcinoma (RCC) 1 2 Active Not Recruiting Treatment Prostate Cancer 1 2 Completed Treatment Colorectal Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 0.89 mg/1 Capsule Oral 1.34 mg/1 Capsule Oral 1340 ?g Capsule Oral 1340 MCG Capsule Oral 890 ?g Capsule Oral 890 MCG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6821987 No 2004-11-23 2022-04-26 US US7166722 No 2007-01-23 2023-11-16 US US11504365 No 2019-11-05 2039-11-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 220-233 https://store.apolloscientific.co.uk/product/tivozanib boiling point (°C) 550.4 ± 50.0 https://www.chemsrc.com/en/cas/475108-18-0_754439.html water solubility <1g/mL https://www.mybiosource.com/inhibitor/tivozanib-av-951/384260 logP 4.31 https://www.chemsrc.com/en/cas/475108-18-0_754439.html Caco2 permeability 0.5 https://www.ema.europa.eu/en/documents/assessment-report/fotivda-epar-public-assessment-report_en.pdf pKa 11.74±0.70 https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82484655.htm - Predicted Properties
Property Value Source Water Solubility 0.0521 mg/mL ALOGPS logP 4.25 ALOGPS logP 4.22 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 8.27 Chemaxon pKa (Strongest Basic) 5.89 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 107.74 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 120.85 m3·mol-1 Chemaxon Polarizability 44.26 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-1000900000-1dfa1d11166c36a4a943 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0532-9002000000-d0a41edc82be03b3c000 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-9001400000-a52f0b88d31018c21c60 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0100-9035400000-5a7bdf826f62e405189f Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00c0-9207600000-fa74583c3bf9d795493d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00lr-9300000000-7c8d7c35cf34cfc85bd5 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 205.81651 predictedDeepCCS 1.0 (2019) [M+H]+ 208.17451 predictedDeepCCS 1.0 (2019) [M+Na]+ 214.26767 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vegf-b-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
- Gene Name
- FLT1
- Uniprot ID
- P17948
- Uniprot Name
- Vascular endothelial growth factor receptor 1
- Molecular Weight
- 150767.185 Da
References
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- Salgia NJ, Zengin ZB, Pal SK: Tivozanib in renal cell carcinoma: a new approach to previously treated disease. Ther Adv Med Oncol. 2020 May 22;12:1758835920923818. doi: 10.1177/1758835920923818. eCollection 2020. [Article]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- Salgia NJ, Zengin ZB, Pal SK: Tivozanib in renal cell carcinoma: a new approach to previously treated disease. Ther Adv Med Oncol. 2020 May 22;12:1758835920923818. doi: 10.1177/1758835920923818. eCollection 2020. [Article]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
- Gene Name
- FLT4
- Uniprot ID
- P35916
- Uniprot Name
- Vascular endothelial growth factor receptor 3
- Molecular Weight
- 152755.94 Da
References
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- Salgia NJ, Zengin ZB, Pal SK: Tivozanib in renal cell carcinoma: a new approach to previously treated disease. Ther Adv Med Oncol. 2020 May 22;12:1758835920923818. doi: 10.1177/1758835920923818. eCollection 2020. [Article]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
- Gene Name
- KIT
- Uniprot ID
- P10721
- Uniprot Name
- Mast/stem cell growth factor receptor Kit
- Molecular Weight
- 109863.655 Da
References
- Kalathil SG, Wang K, Hutson A, Iyer R, Thanavala Y: Tivozanib mediated inhibition of c-Kit/SCF signaling on Tregs and MDSCs and reversal of tumor induced immune suppression correlates with survival of HCC patients. Oncoimmunology. 2020 Sep 30;9(1):1824863. doi: 10.1080/2162402X.2020.1824863. [Article]
- Yalcin S, Lacin S: Impact of tivozanib on patient outcomes in treatment of advanced renal cell carcinoma. Cancer Manag Res. 2019 Aug 16;11:7779-7785. doi: 10.2147/CMAR.S206105. eCollection 2019. [Article]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor binding
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
- Gene Name
- PDGFRB
- Uniprot ID
- P09619
- Uniprot Name
- Platelet-derived growth factor receptor beta
- Molecular Weight
- 123966.895 Da
References
- Motzer RJ, Nosov D, Eisen T, Bondarenko I, Lesovoy V, Lipatov O, Tomczak P, Lyulko O, Alyasova A, Harza M, Kogan M, Alekseev BY, Sternberg CN, Szczylik C, Cella D, Ivanescu C, Krivoshik A, Strahs A, Esteves B, Berkenblit A, Hutson TE: Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013 Oct 20;31(30):3791-9. doi: 10.1200/JCO.2012.47.4940. Epub 2013 Sep 9. [Article]
- Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J: The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007 Jan;92(1):27-34. [Article]
- FDA Approved Drug Products: CUBICIN (daptomycin) injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
- Gene Name
- FLT3
- Uniprot ID
- P36888
- Uniprot Name
- Receptor-type tyrosine-protein kinase FLT3
- Molecular Weight
- 112902.51 Da
References
- Yalcin S, Lacin S: Impact of tivozanib on patient outcomes in treatment of advanced renal cell carcinoma. Cancer Manag Res. 2019 Aug 16;11:7779-7785. doi: 10.2147/CMAR.S206105. eCollection 2019. [Article]
- Motzer RJ, Nosov D, Eisen T, Bondarenko I, Lesovoy V, Lipatov O, Tomczak P, Lyulko O, Alyasova A, Harza M, Kogan M, Alekseev BY, Sternberg CN, Szczylik C, Cella D, Ivanescu C, Krivoshik A, Strahs A, Esteves B, Berkenblit A, Hutson TE: Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013 Oct 20;31(30):3791-9. doi: 10.1200/JCO.2012.47.4940. Epub 2013 Sep 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
- Gene Name
- PDGFRA
- Uniprot ID
- P16234
- Uniprot Name
- Platelet-derived growth factor receptor alpha
- Molecular Weight
- 122668.46 Da
References
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Receptor binding
- Specific Function
- Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. F...
- Gene Name
- PTK6
- Uniprot ID
- Q13882
- Uniprot Name
- Protein-tyrosine kinase 6
- Molecular Weight
- 51833.72 Da
References
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading...
- Gene Name
- TEK
- Uniprot ID
- Q02763
- Uniprot Name
- Angiopoietin-1 receptor
- Molecular Weight
- 125829.005 Da
References
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
- Gene Name
- FGFR1
- Uniprot ID
- P11362
- Uniprot Name
- Fibroblast growth factor receptor 1
- Molecular Weight
- 91866.935 Da
References
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
- Gene Name
- MET
- Uniprot ID
- P08581
- Uniprot Name
- Hepatocyte growth factor receptor
- Molecular Weight
- 155540.035 Da
References
- EMA Assessment Report: Fotivda (tivozanib) oral capsules [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
- EMC Summary of Product Characteristics: Fotivda (tivozanib hydrochloride monohydrate) oral capsules [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: FOTIVDA (tivozanib) capsules, for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Prescribing information indicates that tivozanib is not a substrate for P-glycoprotein, however an in vitro study shows that tivozanib is transported by P-glycoprotein. Clinical significance is unknown.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Tivozanib inhibits BCRP in vitro, but this has not been proven in vivo. Clinical significance is unknown.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Yang D, Kathawala RJ, Chufan EE, Patel A, Ambudkar SV, Chen ZS, Chen X: Tivozanib reverses multidrug resistance mediated by ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Future Oncol. 2014 Aug;10(11):1827-41. doi: 10.2217/fon.13.253. Epub 2013 Dec 3. [Article]
- EMC Summary of Product Characteristics: Fotivda (tivozanib hydrochloride monohydrate) oral capsules [Link]
Drug created at October 20, 2016 20:49 / Updated at March 13, 2021 16:57