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Theophylline (T3D4780)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2014-09-11 05:16:16 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4780
Identification
Common NameTheophylline
ClassSmall Molecule
DescriptionA methylxanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Mechanistically, theophylline acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. Theophylline is marketed under several brand names such as Uniphyl and Theochron, and it is indicated mainly for asthma, bronchospasm, and COPD.
Compound Type
  • Amide
  • Bronchodilator Agent
  • Drug
  • Food Toxin
  • Metabolite
  • Muscle Relaxant, Respiratory
  • Organic Compound
  • Phosphodiesterase Inhibitor
  • Purinergic P1 Receptor Antagonist
  • Synthetic Compound
  • Vasodilator Agent
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,3-dimethyl-7H-purine-2,6-dione
1,3-Dimethylxanthine
Accurbron
Acet-theocin
Aerolate
Aerolate III
Aerolate SR
Aminophylline
Aquaphyllin
Armophylline
Asbron
Asmax
Austyn
Bronkodyl
Bronkodyl SR
Choledyl SA
Constant-T
Diphyllin
Doraphyllin
Duraphyl
Dyspne-Inhal
Elixex
Elixicon
Elixomin
Elixophyllin
Elixophyllin SR
Elixophylline
Euphylline
Euphylong
Labid
Lanophyllin
Liquophylline
Liquorice
Maphylline
Medaphyllin
Nuelin
Optiphyllin
Parkophyllin
Pseudotheophylline
Quibron T/SR
Quibron-T
Quibron-T/Sr
Respbid
Slo-Bid
Slo-Phyllin
Solosin
Somophyllin-Crt
Somophyllin-DF
Somophyllin-T
Spophyllin retard
Sustaire
Synophylate
Synophylate-L.A. Cenules
T-Phyl
Tefamin
Teofilina
Teofyllamin
Teolair
Theacitin
Theal tabl.
Theal tablets
Theo 24
Theo-24
Theo-Dur
Theo-Dur-Sprinkle
Theobid
Theobid Jr.
Theochron
Theocin
Theoclair-SR
Theoclear 80
Theoclear L.A.-130
Theoclear LA
Theoclear-200
Theoclear-80
Theocontin
Theodel
Theodur G
Theofol
Theograd
Theolair
Theolair-Sr
Theolix
Theolixir
Theona P
Theophyl
Theophyl-225
Theophyl-Sr
Theophyline
Theophyllin
Theophylline anhydrous
Theophylline(Anhydrous)
Theophylline-Sr
Theostat 80
Theovent
Uni-Dur
Unifyl
Uniphyl
Uniphyllin
Xanthium
Xantivent
Chemical FormulaC7H8N4O2
Average Molecular Mass180.164 g/mol
Monoisotopic Mass180.065 g/mol
CAS Registry Number58-55-9
IUPAC Name1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
Traditional Nametheophylline
SMILESCN1C2=C(N=CN2)C(=O)N(C)C1=O
InChI IdentifierInChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9)
InChI KeyInChIKey=ZFXYFBGIUFBOJW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents
Substituents
  • Xanthine
  • 6-oxopurine
  • Purinone
  • Alkaloid or derivatives
  • Pyrimidone
  • Pyrimidine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Lactam
  • Urea
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Medulla
  • Brain
  • Epidermis
  • Fibroblasts
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Neutrophil
  • Pancreas
  • Placenta
  • Platelet
  • Skeletal Muscle
  • Stratum Corneum
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Caffeine MetabolismSMP00028 map00232
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point273°C
Boiling PointNot Available
Solubility7360 mg/L (at 25°C)
LogP-0.02
Predicted Properties
PropertyValueSource
Water Solubility22.9 g/LALOGPS
logP-0.26ALOGPS
logP-0.77ChemAxon
logS-0.9ALOGPS
pKa (Strongest Acidic)7.82ChemAxon
pKa (Strongest Basic)-0.78ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity44.93 m³·mol⁻¹ChemAxon
Polarizability16.86 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-0f79-6970000000-224461ad62a44dbdf8602014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001j-7900000000-a08735d528e7387524292017-09-12View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-001i-0900000000-d0882f7d959c726e76232017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001i-9700000000-8d0e1898a6571fbca10a2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0f79-6970000000-224461ad62a44dbdf8602017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0fka-4900000000-878cab6882fd80efba3b2017-07-27View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-0900000000-0092516012d6a2a93b312012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-4900000000-dcf52c18a6996f412b1a2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00kf-9000000000-09089337909892ef44cb2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (Unknown) , Positivesplash10-001j-7900000000-a08735d528e7387524292012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - CI-B (Unknown) , Positivesplash10-001i-0900000000-d0882f7d959c726e76232012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-004i-0900000000-c4943571126a44bb9e5a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-004i-0900000000-bc12ce29acd02fa749b82012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-03k9-0900000000-d63f60043f186fbb9bc02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-070l-4900000000-d293ab2fa6199dbaf97a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-05ru-9400000000-dde4775588d52c83806f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-004i-0900000000-556e382f583d610ef1f02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-004i-0900000000-89e34f5158856ba334692012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-03k9-0900000000-65a6897d72954e875b002012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-070l-4900000000-df16604bd6c40cee8f242012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-05r3-9500000000-39a721dcecc86ed955072012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-001i-1900000000-e67ff7ef9a955b90eb3f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-001i-3900000000-1870952d98dbba22ace82012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-7900000000-dc0e9606776c43a7823f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-014j-9300000000-2c4c6490dda3ed3b563f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-014i-9000000000-26a6c0c23a465afdcde12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-01q9-1900000000-b11ca3441bb29fef19062012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-0002-9400000000-63726fe0b49a9dc6ba7e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-9100000000-139f765bc9b5855960c62012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-00di-9000000000-88b5cb393b960973ac642012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00yi-9000000000-1ebbddce3c71339725462012-08-31View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00lr-9500000000-2c8464c2fe84464c207f2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureTheophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.
Mechanism of ToxicityTheophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.
MetabolismHepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. Route of Elimination: Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults. Half Life: 8 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (14)
Uses/SourcesFor the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include seizures, arrhythmias, and GI effects.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00277
HMDB IDHMDB01889
PubChem Compound ID2153
ChEMBL IDCHEMBL190
ChemSpider ID2068
KEGG IDC07130
UniProt IDNot Available
OMIM ID
ChEBI ID28177
BioCyc IDTHF-GLU-N
CTD IDNot Available
Stitch IDNot Available
PDB IDTEP
ACToR IDNot Available
Wikipedia LinkTheophylline
References
Synthesis Reference

Nicolae S. Bodor, Kenneth B. Sloan, Yu-Neng Kuo, “Method for synthesizing certain selected pro-drug forms of theophylline.” U.S. Patent US4000132, issued January, 1956.

MSDSLink
General References
  1. Bath PM: Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke. Cochrane Database Syst Rev. 2004;(3):CD000211. [15266427 ]
  2. Yasui K, Agematsu K, Shinozaki K, Hokibara S, Nagumo H, Yamada S, Kobayashi N, Komiyama A: Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions. J Leukoc Biol. 2000 Aug;68(2):194-200. [10947063 ]
  3. Gerbershagen MU, Fiege M, Weisshorn R, Kolodzie K, Wappler F: [Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2004 Mar;39(3):147-52. [15042504 ]
  4. Mahomed AG, Theron AJ, Anderson R, Feldman C: Anti-oxidative effects of theophylline on human neutrophils involve cyclic nucleotides and protein kinase A. Inflammation. 1998 Dec;22(6):545-57. [9824770 ]
  5. Andreas S, Reiter H, Luthje L, Delekat A, Grunewald RW, Hasenfuss G, Somers VK: Differential effects of theophylline on sympathetic excitation, hemodynamics, and breathing in congestive heart failure. Circulation. 2004 Oct 12;110(15):2157-62. Epub 2004 Oct 4. [15466632 ]
  6. Yano Y, Yoshida M, Hoshino S, Inoue K, Kida H, Yanagita M, Takimoto T, Hirata H, Kijima T, Kumagai T, Osaki T, Tachibana I, Kawase I: Anti-fibrotic effects of theophylline on lung fibroblasts. Biochem Biophys Res Commun. 2006 Mar 17;341(3):684-90. Epub 2006 Jan 18. [16430859 ]
  7. Mohiuddin AA, Bath FJ, Bath PM: Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke. Cochrane Database Syst Rev. 2000;(2):CD000211. [10796327 ]
  8. Mehta R, Weinberger B, Usmani SS, Wapnir RA, Harper RG: Theophylline alters neutrophil function in preterm infants. Biol Neonate. 2002;81(3):176-81. [11937723 ]
  9. Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT: Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol. 2005 Feb;16(2):452-8. Epub 2004 Dec 8. [15590762 ]
  10. Spoelstra FM, Berends C, Dijkhuizen B, de Monchy JG, Kauffman HF: Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro. Eur Respir J. 1998 Sep;12(3):585-91. [9762784 ]
  11. Bailey DN: Relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro. J Anal Toxicol. 1997 Jan-Feb;21(1):1-4. [9013284 ]
  12. Teplinskaia LE, Filichkina NS, Matevosova KS: [Efficiency of treatment of uveitis with the drug superlymph]. Vestn Oftalmol. 2005 Jul-Aug;121(4):22-6. [16223038 ]
  13. Yoshiike T, Aikawa Y, Sindhvananda J, Suto H, Nishimura K, Kawamoto T, Ogawa H: Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline. J Dermatol Sci. 1993 Apr;5(2):92-6. [8357787 ]
  14. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Adenosine receptor A2b
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
ADORA2B
Uniprot ID:
P29275
Molecular Weight:
36332.655 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV: Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res. 2006 May 1;70(2):308-14. Epub 2006 Feb 23. [16545350 ]
  3. Phelps PT, Anthes JC, Correll CC: Characterization of adenosine receptors in the human bladder carcinoma T24 cell line. Eur J Pharmacol. 2006 Apr 24;536(1-2):28-37. Epub 2006 Mar 3. [16581066 ]
  4. Fozard JR, Baur F, Wolber C: Antagonist pharmacology of adenosine A2B receptors from rat, guinea pig and dog. Eur J Pharmacol. 2003 Aug 15;475(1-3):79-84. [12954362 ]
  5. Holgate ST: The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma. Br J Pharmacol. 2005 Aug;145(8):1009-15. [15980878 ]
  6. Daly JW, Jacobson KA, Ukena D: Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63. [3588607 ]
Target Details
2. cAMP-specific 3',5'-cyclic phosphodiesterase 4A
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
References
  1. Wang K, Chen JQ, Chen Z, Chen JC: Inhibition of human phosphodiesterase 4A expressed in yeast cell GL62 by theophylline, rolipram, and acetamide-45. Acta Pharmacol Sin. 2002 Nov;23(11):1013-7. [12421478 ]
  2. Haider S: Cyclic AMP level and phosphodiesterase activity during 17alpha,20beta-dihydroxy-4-pregnen-3-one induction and theophylline inhibition of oocyte maturation in the catfish, Clarias batrachus. Comp Biochem Physiol A Mol Integr Physiol. 2003 Feb;134(2):267-74. [12547256 ]
  3. Rickards KJ, Andrews MJ, Waterworth TH, Alexander GB, Cunningham FM: Differential effects of phosphodiesterase inhibitors on platelet activating factor (PAF)- and adenosine diphosphate (ADP)-induced equine platelet aggregation. J Vet Pharmacol Ther. 2003 Aug;26(4):277-82. [12887610 ]
  4. Usta C, Sadan G, Tuncel B: The effect of the indomethacin on phosphodiesterase inhibitors mediated responses in isolated trachea preparations. Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):137-41. [15253881 ]
  5. Lee JM, Zemans RL, Hejazi M, Chin BB, Ladenson PW, Caturegli P: Modulation of thyroidal radioiodine uptake by theophylline. Exp Mol Pathol. 2004 Oct;77(2):116-20. [15351234 ]
Target Details
3. cGMP-inhibited 3',5'-cyclic phosphodiesterase A
General Function:
Metal ion binding
Specific Function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular Weight:
124978.06 Da
References
  1. Rickards KJ, Andrews MJ, Waterworth TH, Alexander GB, Cunningham FM: Differential effects of phosphodiesterase inhibitors on platelet activating factor (PAF)- and adenosine diphosphate (ADP)-induced equine platelet aggregation. J Vet Pharmacol Ther. 2003 Aug;26(4):277-82. [12887610 ]
  2. Wu BN, Lin RJ, Lo YC, Shen KP, Wang CC, Lin YT, Chen IJ: KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol. 2004 Aug;142(7):1105-14. Epub 2004 Jul 5. [15237094 ]
  3. Kajikawa S, Kigami D, Nakayama H, Doi K: Changes in submaxillary gland gene expression in F344 rats by multiple dosing of theophylline. Exp Anim. 2006 Apr;55(2):143-6. [16651698 ]
Target Details
4. Histone deacetylase 2
General Function:
Transcription factor binding
Specific Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.
Gene Name:
HDAC2
Uniprot ID:
Q92769
Molecular Weight:
55363.855 Da
References
  1. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8921-6. Epub 2002 Jun 17. [12070353 ]
  2. Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ: Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med. 2004 Sep 6;200(5):689-95. Epub 2004 Aug 30. [15337792 ]
Target Details
5. cAMP-specific 3',5'-cyclic phosphodiesterase 4B
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular Weight:
83342.695 Da
References
  1. Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet. 2005 Jan 8-14;365(9454):167-75. [15639300 ]
Target Details
6. cGMP-specific 3',5'-cyclic phosphodiesterase
General Function:
Metal ion binding
Specific Function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
Gene Name:
PDE5A
Uniprot ID:
O76074
Molecular Weight:
99984.14 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
7. Transcription factor E2F1
General Function:
Transcription factor binding
Specific Function:
Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812).
Gene Name:
E2F1
Uniprot ID:
Q01094
Molecular Weight:
46919.28 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.715 uMATG_E2F_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
8. Adenosine receptor A2a
General Function:
Identical protein binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
ADORA2A
Uniprot ID:
P29274
Molecular Weight:
44706.925 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.37 uMNVS_GPCR_hAdoRA2aNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
9. Adenosine receptor A1
General Function:
Purine nucleoside binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
ADORA1
Uniprot ID:
P30542
Molecular Weight:
36511.325 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.43 uMNVS_GPCR_hAdoRA1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]