General
Preferred name
DOXOFYLLINE
Synonyms
Doxophylline ()
Ansimar ()
NSC-759645 ()
Dioxyfilline ()
Ventax ()
ABC 12/3 ()
Synasma ()
Doxofilina ()
P&D ID
PD001310
CAS
69975-86-6
Tags
available
drug
Drug indication
Asthma
Bronchodilator
Drug Status
experimental
approved
investigational
Max Phase
3.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation. ; ; The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking [A31646]. Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed [A31646]. Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation. ; ; There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study [A31646]. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro [A31643].Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.
PHARMACODYNAMICS
Doxofylline is a methylxanthine bronchodilator with potent bronchodilator activity comparable to that of theophylline. In animal studies, doxofylline demonstrated to attenuate bronchoconstriction, inflammatory actions and the release of thromboxane A2 (TXA2) when challenged with platelet-activating factor [L1169]. ; ; Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A and A2B receptors are reported to be all higher than 100 µM [A31643]. It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations [A31642]. A study demonstrated that doxofylline interacts with β2-adrenoceptors to induce blood vessel relaxation and airway smooth muscle relaxation. In dog studies, doxofylline decreased airway responsiveness at a dose that did not affect heart rate and respiratory rate [A31643].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
19
Cayman Chemical Bioactives
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
Natural product-based probes and drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
29
Molecular Weight
266.1
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
0
Rotatable Bonds
2
Ring Count
3
Aromatic Ring Count
2
cLogP
-1.19
TPSA
80.28
Fraction CSP3
0.55
Chiral centers
0.0
Largest ring
6.0
QED
0.68
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Metabolism
GPCR/G protein
Immunology/Inflammation
Metabolic Enzyme/Protease
NF-κB
Target
PDE
ADORA1, PDE4A, PDE4B, PDE4C, PDE4D
Adenosine Receptor
Phosphodiesterase (PDE)
Reactive Oxygen Species
Member status
member
MOA
Adenosine A1 Antagonists
Adenosine Receptor antagonist
Indication
asthma
Biosynthetic Origin
Nucleoside (Nucleobase)
Therapeutic Indication
Bronchodilator
Therapeutic Class
Respiratory
Source data
