Identification
- Generic Name
- Dovitinib
- DrugBank Accession Number
- DB05928
- Background
Dovitinib is an orally active small molecule that exhibits potent inhibitory activity against multiple RTKs involved in tumor growth and angiogenesis. Preclinical data show that dovitinib works to inhibit multiple kinases associated with different cancers, including acute myeloid leukemia (AML) and multiple myeloma. Chiron currently has three ongoing Phase I clinical trials for dovitinib.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Dovitinib (DB05928)
- Weight
- Average: 392.438
Monoisotopic: 392.176087483 - Chemical Formula
- C21H21FN6O
- Synonyms
- Dovitinib
- External IDs
- TKI-258
Pharmacology
- Indication
Investigated for use/treatment in multiple myeloma and solid tumors.
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.- 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
Not Available
- Mechanism of action
Unlike many kinase inhibitors that only target vascular endothelial growth factor (VEGF), Dovitinib inhibits receptors in the fibroblast growth factor (FGF ) pathway, as well as VEGF and platelet-derived growth factor (PDGF). FGF receptor tyrosine kinase inhibition is potentially of therapeutic significance to a group of myeloma patients whose cancer cells express high levels of surface FGF receptors.
Target Actions Organism UNuclear receptor subfamily 1 group I member 2 suppressorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- 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
Not Available
- 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 The metabolism of Abemaciclib can be decreased when combined with Dovitinib. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Dovitinib. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Dovitinib. Acemetacin The metabolism of Acemetacin can be decreased when combined with Dovitinib. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Dovitinib. - Food Interactions
- Not Available
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 Dovitinib lactate hydrate 69VKY8P7EA 915769-50-5 QDPVYZNVVQQULH-TYOUJGAFSA-N
Categories
- Drug Categories
- BCRP/ABCG2 Inducers
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- P-glycoprotein inhibitors
- Quinolines
- Tyrosine Kinase Inhibitors
- UGT1A3 Inhibitors
- UGT2B7 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- N-arylpiperazines
- Alternative Parents
- 4-aminoquinolines / Haloquinolines / Hydroquinolones / Hydroquinolines / Benzimidazoles / Dialkylarylamines / Aminopyridines and derivatives / N-methylpiperazines / Pyridinones / Aryl fluorides show 12 more
- Substituents
- 4-aminoquinoline / Amine / Aminopyridine / Aminoquinoline / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- I35H55G906
- CAS number
- 405169-16-6
- InChI Key
- PIQCTGMSNWUMAF-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H21FN6O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)
- IUPAC Name
- 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-1,3-benzodiazol-2-yl]-1,2-dihydroquinolin-2-one
- SMILES
- CN1CCN(CC1)C1=CC=C2N=C(NC2=C1)C1=C(N)C2=C(NC1=O)C=CC=C2F
References
- General References
- Xin X, Abrams TJ, Hollenbach PW, Rendahl KG, Tang Y, Oei YA, Embry MG, Swinarski DE, Garrett EN, Pryer NK, Trudel S, Jallal B, Mendel DB, Heise CC: CHIR-258 is efficacious in a newly developed fibroblast growth factor receptor 3-expressing orthotopic multiple myeloma model in mice. Clin Cancer Res. 2006 Aug 15;12(16):4908-15. [Article]
- Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK: CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005 Apr 1;105(7):2941-8. Epub 2004 Dec 14. [Article]
- External Links
- PubChem Compound
- 9977819
- PubChem Substance
- 347827750
- ChemSpider
- 11530944
- BindingDB
- 25118
- ChEMBL
- CHEMBL522892
- ZINC
- ZINC000003816310
- PDBe Ligand
- 38O
- Wikipedia
- Fibroblast_growth_factor_receptor_1
- PDB Entries
- 4tyi / 5a46 / 5am6 / 5am7 / 5owq / 7akg / 7qq6
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 Completed Treatment Metastatic Renal Cell Carcinoma ( mRCC) 1 2 Completed Treatment ACC / Metastatic Adenoid Cystic Carcinoma of the Salivary Glands / Recurrent Adenoid Cystic Carcinoma of the Salivary Glands / Salivary Gland Cancers 1 2 Completed Treatment Adenocarcinoma, Scirrhous / Linitis Plastica / Neoplasm / Neoplasm of Stomach / Neoplasms by Site / Stomach Diseases 1 2 Completed Treatment Adenoid Cystic Carcinoma 2 2 Completed Treatment Adrenocortical Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.137 mg/mL ALOGPS logP 2.34 ALOGPS logP 1.35 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 8.56 Chemaxon pKa (Strongest Basic) 7.87 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 90.28 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 112.36 m3·mol-1 Chemaxon Polarizability 42.46 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No 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 splash10-0006-0009000000-b771d272bbea73295dec Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00xr-5009000000-b27979f35488dc869f83 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0009000000-62a41d6da4a8a748ce83 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00xr-2009000000-eff4cd3dd0e9cbb903e3 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0019-1009000000-88e8533046ab00c99ccc Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0ul0-1159000000-1c42373313f428886a58 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]- 187.66832 predictedDeepCCS 1.0 (2019) [M+H]+ 190.04321 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.20439 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Suppressor
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Vitamin d 24-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 oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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 oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Das M, Padda SK, Frymoyer A, Zhou L, Riess JW, Neal JW, Wakelee HA: Dovitinib and erlotinib in patients with metastatic non-small cell lung cancer: A drug-drug interaction. Lung Cancer. 2015 Sep;89(3):280-6. doi: 10.1016/j.lungcan.2015.06.011. Epub 2015 Jun 22. [Article]
- DOVITINIB LACTATE Multikinase Inhibitor Antiongiogenic Agent Oncolytic [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60694.12 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
- Gene Name
- ABCC3
- Uniprot ID
- O15438
- Uniprot Name
- Canalicular multispecific organic anion transporter 2
- Molecular Weight
- 169341.14 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- 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
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76709.98 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Weiss J, Theile D, Dvorak Z, Haefeli WE: Interaction potential of the multitargeted receptor tyrosine kinase inhibitor dovitinib with drug transporters and drug metabolising enzymes assessed in vitro. Pharmaceutics. 2014 Dec 16;6(4):632-50. doi: 10.3390/pharmaceutics6040632. [Article]
Drug created at November 18, 2007 18:28 / Updated at January 14, 2023 19:03