NAV

TG-100801

Identification

Generic Name
TG-100801
DrugBank Accession Number
DB05075
Background

TG100801 is a topically applied kinase inhibitor in macular degeneration patients. It is administered noninvasively as an eye drop and is designed to suppress VEGF mediated leakage and additional kinase targets associated with inflammation, edema, and angiogenesis which are the pathological hallmarks of AMD and other back of the eye diseases including diabetic macular edema and proliferative diabetic retinopathy.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 580.09
Monoisotopic: 579.2037175
Chemical Formula
C33H30ClN5O3
Synonyms
Not Available
External IDs
  • TG 100801
  • TG-100801
  • TG100801
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Pharmacology

Indication

Investigated for use/treatment in macular degeneration.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.

Mechanism of action

TG100801 is the first topically applied, multitargeted vascular endothelial growth factor receptor (VEGFR)/Src kinase inhibitor to advance into the clinic. TG100801 significantly reduced VEGF mediated retinal leakage and choroidal neovascularization in relevant pre-clinical models of macular degeneration. In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.

TargetActionsOrganism
UVascular endothelial growth factor receptor 1Not AvailableHumans
UVascular endothelial growth factor receptor 2Not AvailableHumans
UVascular endothelial growth factor receptor 3Not AvailableHumans
UTyrosine-protein kinase CSKNot 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
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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
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as depsides and depsidones. These are polycyclic compounds that is either a polyphenolic compound composed of two or more monocyclic aromatic units linked by an ester bond (depside), or a compound containing the depsidone structure (depsidone).
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Depsides and depsidones
Sub Class
Not Available
Direct Parent
Depsides and depsidones
Alternative Parents
Phenol esters / Benzoic acid esters / Phenoxy compounds / Phenol ethers / Aniline and substituted anilines / Benzoyl derivatives / Alkyl aryl ethers / Aminotriazines / Chlorobenzenes / 1,2,4-triazines
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Substituents
1,2,4-triazine / Alkyl aryl ether / Amine / Amino acid or derivatives / Aminotriazine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle
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Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
1VZO7A0J9S
CAS number
867331-82-6
InChI Key
JMGXJHWTVBGOKG-UHFFFAOYSA-N
InChI
InChI=1S/C33H30ClN5O3/c1-22-19-24(28-21-27(13-14-29(28)34)42-32(40)23-7-3-2-4-8-23)20-30-31(22)36-33(38-37-30)35-25-9-11-26(12-10-25)41-18-17-39-15-5-6-16-39/h2-4,7-14,19-21H,5-6,15-18H2,1H3,(H,35,36,38)
IUPAC Name
4-chloro-3-[5-methyl-3-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)-1,2,4-benzotriazin-7-yl]phenyl benzoate
SMILES
CC1=C2N=C(NC3=CC=C(OCCN4CCCC4)C=C3)N=NC2=CC(=C1)C1=CC(OC(=O)C2=CC=CC=C2)=CC=C1Cl

References

General References
Not Available
PubChem Compound
11973736
PubChem Substance
347827709
ChemSpider
10147091
BindingDB
97971
ChEMBL
CHEMBL403989
ZINC
ZINC000029136020

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization (CNV)1
1CompletedTreatmentDiabetic Retinopathy (DR) / Macular Degeneration1

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
PropertyValueSource
Water Solubility0.00167 mg/mLALOGPS
logP6.62ALOGPS
logP7.64Chemaxon
logS-5.5ALOGPS
pKa (Strongest Acidic)13.33Chemaxon
pKa (Strongest Basic)9.03Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area89.47 Å2Chemaxon
Rotatable Bond Count10Chemaxon
Refractivity165.53 m3·mol-1Chemaxon
Polarizability63.93 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0900020000-58c5ea070e20d4feb4bb
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00b9-6500590000-deceb133c4159631f879
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900130000-6afd7f4e87ad9f711d72
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-003r-9003360000-b6b3f35cf533e807f8a5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9201210000-5753ba5eaedb683ee91d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pc0-9500030000-70b9c302be693c0a74b6
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-222.33809
predicted
DeepCCS 1.0 (2019)
[M+H]+224.73366
predicted
DeepCCS 1.0 (2019)
[M+Na]+231.00554
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Vascular endothelial growth factor receptor 1
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
Details2. Vascular endothelial growth factor receptor 2
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
Details3. Vascular endothelial growth factor receptor 3
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
Details4. Tyrosine-protein kinase CSK
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C...
Gene Name
CSK
Uniprot ID
P41240
Uniprot Name
Tyrosine-protein kinase CSK
Molecular Weight
50703.975 Da

Drug created at October 21, 2007 22:23 / Updated at June 12, 2020 16:52