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Identification
NameABT-869
Accession NumberDB06080
TypeSmall Molecule
GroupsInvestigational
DescriptionABT-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. ABT-869 is intended for the treatment of hematologic malignancies and the solid tumors.
Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIINot Available
CAS numberNot Available
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Pharmacology
IndicationInvestigated for use/treatment in leukemia (myeloid), myelodysplastic syndrome, and solid tumors.
Structured Indications Not Available
PharmacodynamicsABT-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 actionABT-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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Receptor-type tyrosine-protein kinase FLT3ProteinunknownNot AvailableHumanP36888 details
Vascular endothelial growth factor receptor 1ProteinunknownNot AvailableHumanP17948 details
Vascular endothelial growth factor receptor 2ProteinunknownNot AvailableHumanP35968 details
Vascular endothelial growth factor receptor 3ProteinunknownNot AvailableHumanP35916 details
Mast/stem cell growth factor receptor KitProteinunknownNot AvailableHumanP10721 details
Macrophage colony-stimulating factor 1 receptorProteinunknownNot AvailableHumanP07333 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:18160102 ]
  2. 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. [PubMed:16648572 ]
  3. 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. [PubMed:16648571 ]
External LinksNot Available
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET featuresNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Taxonomy
ClassificationNot classified

Targets

Kind
Protein
Organism
Human
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. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or...
Gene Name:
FLT3
Uniprot ID:
P36888
Molecular Weight:
112902.51 Da
Kind
Protein
Organism
Human
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 survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation ...
Gene Name:
FLT1
Uniprot ID:
P17948
Molecular Weight:
150767.185 Da
Kind
Protein
Organism
Human
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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
Molecular Weight:
151525.555 Da
Kind
Protein
Organism
Human
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 cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced pr...
Gene Name:
FLT4
Uniprot ID:
P35916
Molecular Weight:
152755.94 Da
Kind
Protein
Organism
Human
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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
Molecular Weight:
109863.655 Da
Kind
Protein
Organism
Human
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 cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in inn...
Gene Name:
CSF1R
Uniprot ID:
P07333
Molecular Weight:
107982.955 Da
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Drug created on November 18, 2007 11:29 / Updated on August 17, 2016 12:24