Identification
- Generic Name
- Linifanib
- DrugBank Accession Number
- DB06080
- Background
Linifanib (ABT-869) is a small molecule vascular endothelial growth factor (VEGF) receptor-based kinase inhibitor that is designed to suppress tumor growth by preventing the formation of new blood vessels that supply the tumor with oxygen and nutrients and by inhibiting key angiogenic signaling pathways. Linifanib is intended for the treatment of hematologic malignancies and the solid tumors.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Linifanib (DB06080)
- Weight
- Average: 375.407
Monoisotopic: 375.149538383 - Chemical Formula
- C21H18FN5O
- Synonyms
- ABT-869
- Linifanib
- External IDs
- A-741439
- RG-3635
Pharmacology
- Indication
Investigated for use/treatment in leukemia (myeloid), myelodysplastic syndrome, 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
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
ABT-869 was effective in a broad range of cancers including small cell lung carcinoma, colon carcinoma, breast carcinoma and MV4-11 tumors in vitro and in vivo. ABT-869 induced significant apoptosis in cells with FLT3 mutation in vitro (IC50 value of 4 nM) and profound anti-leukemic effect in a mouse xenograft model. However, in vitro ABT-869 only shows minimal cytotoxic effect on AML cells with wild-type FLT3. Based on the preclinical studies suggesting the role of VEGF pathways in leukemogenesis, it is likely that the anti-leukemic effect of ABT-869 will be best evaluated in vivo.
- Mechanism of action
ABT-869, a multi-targeted receptor tyrosine kinase inhibitor, has been shown to inhibit of all members of the VEGF and PDGF receptor families (e.g., KDR IC50 value of 4 nM), and have less activity (IC50 values >1 µM) against unrelated receptor tyrosine kinases, soluble tyrosine kinases and serine/threonine kinases. In addition, it exhibits potent anti-proliferative and apoptotic effects on tumor cells dependent on mutant, constitutively active, FLT3 and KIT kinases.
Target Actions Organism UReceptor-type tyrosine-protein kinase FLT3 Not Available Humans UVascular endothelial growth factor receptor 1 Not Available Humans UVascular endothelial growth factor receptor 2 Not Available Humans UVascular endothelial growth factor receptor 3 Not Available Humans UMast/stem cell growth factor receptor Kit Not Available Humans UMacrophage colony-stimulating factor 1 receptor Not Available Humans - 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.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- CO93X137CW
- CAS number
- 796967-16-3
- InChI Key
- MPVGZUGXCQEXTM-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H18FN5O/c1-12-5-10-16(22)18(11-12)25-21(28)24-14-8-6-13(7-9-14)15-3-2-4-17-19(15)20(23)27-26-17/h2-11H,1H3,(H3,23,26,27)(H2,24,25,28)
- IUPAC Name
- 3-[4-(3-amino-1H-indazol-4-yl)phenyl]-1-(2-fluoro-5-methylphenyl)urea
- SMILES
- CC1=CC(NC(=O)NC2=CC=C(C=C2)C2=C3C(N)=NNC3=CC=C2)=C(F)C=C1
References
- General References
- Zhou J, Khng J, Jasinghe VJ, Bi C, Neo CH, Pan M, Poon LF, Xie Z, Yu H, Yeoh AE, Lu Y, Glaser KB, Albert DH, Davidsen SK, Chen CS: In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor. Leuk Res. 2008 Jul;32(7):1091-100. Epub 2007 Dec 26. [Article]
- Guo J, Marcotte PA, McCall JO, Dai Y, Pease LJ, Michaelides MR, Davidsen SK, Glaser KB: Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors. Mol Cancer Ther. 2006 Apr;5(4):1007-13. [Article]
- Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS, Wang B, Bukofzer GT, Wang YC, Stavropoulos JA, Hartandi K, Niquette AL, Soni N, Johnson EF, McCall JO, Bouska JJ, Luo Y, Donawho CK, Dai Y, Marcotte PA, Glaser KB, Michaelides MR, Davidsen SK: Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006. [Article]
- External Links
- PubChem Substance
- 347910329
- ChemSpider
- 9660475
- BindingDB
- 21079
- ChEBI
- 91435
- ChEMBL
- CHEMBL223360
- ZINC
- ZINC000006718813
- Wikipedia
- Linifanib
Clinical Trials
- Clinical Trials
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 0.00546 mg/mL ALOGPS logP 4.2 ALOGPS logP 4.51 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 10.4 Chemaxon pKa (Strongest Basic) 3.37 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 95.83 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 111.48 m3·mol-1 Chemaxon Polarizability 38.98 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 No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- 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 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein homodimerization activity
- Specific Function
- Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor ...
- Gene Name
- CSF1R
- Uniprot ID
- P07333
- Uniprot Name
- Macrophage colony-stimulating factor 1 receptor
- Molecular Weight
- 107982.955 Da
Drug created at November 18, 2007 18:29 / Updated at April 07, 2021 09:52