Identification

Name
XL999
Accession Number
DB05014
Type
Small Molecule
Groups
Investigational
Description

XL999 has the potential to provide benefit to patients with lung cancer and acute myelogenous leukemia. XL999 is a new chemical entity that inhibits a spectrum of receptor tyrosine kinases (RTKs) with growth promoting and angiogenic properties, including FGFR 1/3, PDGFRα/β, VEGFR2/KDR, KIT, and FLT3. XL999 also inhibits FLT4 and SRC. XL999 has the potential to prevent tumor growth — both directly by a novel effect on tumor cell proliferation and indirectly through inhibition of the host angiogenic response. XL999 induces a cell-cycle block by a mechanism distinct from those previously identified and exhibits broad antitumor activity in xenograft models.

Synonyms
Not Available
Categories
Not Available
UNII
Not Available
CAS number
921206-68-0
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified), lung cancer, and solid tumors.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

XL999 is a potent inhibitor of key receptor tyrosine kinases implicated in the development and maintenance of tumor vasculature and in the proliferation of some tumor cells. It inhibits FGFR1, FGFR3, RET, VEGFR2 and PDGFR, and is also a potent inhibitor of FLT3, an important driver of leukemia cell proliferation in some patients with acute myelogenous leukemia (AML). XL999 exhibited excellent activity in target-specific cellular functional assays.

TargetActionsOrganism
UFibroblast growth factor receptor 3Not AvailableHuman
UFibroblast growth factor receptor 1Not AvailableHuman
UVascular endothelial growth factor receptor 2Not AvailableHuman
UReceptor-type tyrosine-protein kinase FLT3Not AvailableHuman
UPlatelet-derived growth factor receptor betaNot AvailableHuman
URET proto-oncogeneNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Substance
347909892

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Malignancies1
1CompletedTreatmentCancers1
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentCancer, Ovarian1
2TerminatedTreatmentColorectal Cancers1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentRenal Cell Adenocarcinoma1
Not AvailableNo Longer AvailableNot AvailableAdvanced Malignancy1

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
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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 cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
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 ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
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 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
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Not Available
Gene Name
RET
Uniprot ID
O43519
Uniprot Name
RET proto-oncogene
Molecular Weight
2129.3 Da

Drug created on October 21, 2007 16:23 / Updated on November 06, 2017 06:45