Identification

Generic Name
XL999
DrugBank Accession Number
DB05014
Background

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.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication

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

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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Avoid life-threatening adverse drug events & improve clinical decision support.
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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 AvailableHumans
UFibroblast growth factor receptor 1Not AvailableHumans
UVascular endothelial growth factor receptor 2Not AvailableHumans
UReceptor-type tyrosine-protein kinase FLT3Not AvailableHumans
UPlatelet-derived growth factor receptor betaNot AvailableHumans
URET proto-oncogeneNot AvailableHumans
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
Adverseeffects
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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
Not Available
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Not Available
CAS number
921206-68-0
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
Not Available
PubChem Substance
347909892

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentAcute Myeloid Leukemia (AML)1
2TerminatedTreatmentColorectal Carcinoma (CRC)1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2TerminatedTreatmentOvarian Cancer1
2TerminatedTreatmentRenal Cell Adenocarcinoma1
1CompletedTreatmentAdvanced Malignancies1
1CompletedTreatmentMalignancies1
1TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
Not AvailableNo Longer AvailableNot AvailableAdvanced Malignancies1

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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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
Humans
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
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 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
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
Humans
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 at October 21, 2007 22:23 / Updated at June 12, 2020 16:52