Theophylline
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Basic Info
| Common Name | Theophylline(F05509) |
| 2D Structure | |
| Description | A 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. |
| FRCD ID | F05509 |
| CAS Number | 58-55-9 |
| PubChem CID | 2153 |
| Formula | C7H8N4O2 |
| IUPAC Name | 1,3-dimethyl-7H-purine-2,6-dione |
| InChI Key | ZFXYFBGIUFBOJW-UHFFFAOYSA-N |
| InChI | InChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9) |
| Canonical SMILES | CN1C2=C(C(=O)N(C1=O)C)NC=N2 |
| Isomeric SMILES | CN1C2=C(C(=O)N(C1=O)C)NC=N2 |
| Wikipedia | Theophylline |
| Synonyms |
1,3-Dimethylxanthine
theophylline
58-55-9
Elixophyllin
Theophyllin
Theolair
Nuelin
Theophylline anhydrous
Respbid
Theocin
|
| Classifies |
Predicted: Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Imidazopyrimidines |
| Subclass | Purines and purine derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Xanthines |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 180.167 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 0 |
| Complexity | 267 |
| Monoisotopic Mass | 180.065 |
| Exact Mass | 180.065 |
| XLogP | 0 |
| Formal Charge | 0 |
| Heavy Atom Count | 13 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9902 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.6172 |
| P-glycoprotein Substrate | Non-substrate | 0.7281 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8939 |
| Non-inhibitor | 0.9110 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8807 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7079 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7738 |
| CYP450 2D6 Substrate | Non-substrate | 0.9117 |
| CYP450 3A4 Substrate | Non-substrate | 0.5974 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9933 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9827 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9895 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9616 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9956 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8819 |
| Non-inhibitor | 0.8927 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9447 |
| Fish Toxicity | Low FHMT | 0.7912 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7458 |
| Honey Bee Toxicity | Low HBT | 0.8027 |
| Biodegradation | Ready biodegradable | 0.5942 |
| Acute Oral Toxicity | II | 0.7269 |
| Carcinogenicity (Three-class) | Non-required | 0.7077 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.4524 | LogS |
| Caco-2 Permeability | 1.3897 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.7898 | LD50, mol/kg |
| Fish Toxicity | 2.1827 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.2261 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Bio-detheobromination of cocoa pod husks: reduction of ochratoxin A content without change in nutrient profile. | Microb Cell Fact | 2018 May 19 | 29778093 |
| Source estimation of pharmaceuticals based on catchment population and in-stream attenuation in Yodo River watershed, Japan. | Sci Total Environ | 2018 Feb 15 | 29751447 |
| Decrease of the affinity of theophylline bind to serum proteins induced by flavonoids and their synergies on protein conformation. | Int J Biol Macromol | 2018 Feb | 28947221 |
| Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3. | Am J Physiol Renal Physiol | 2015 Jun 15 | 25925253 |
| The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-RelatedNeurodegenerative Disorders. | Curr Top Med Chem | 2015 | 26059354 |
| Comparison of selected physico-chemical properties of calcium alginate films prepared by two different methods. | Int J Pharm | 2014 Oct 1 | 24974988 |
| Differential effects of bitter compounds on the taste transduction channels TRPM5and IP3 receptor type 3. | Chem Senses | 2014 May | 24452633 |
| Aqueous and hydro-alcoholic media effects on polyols. | Colloids Surf B Biointerfaces | 2013 Nov 1 | 23777788 |
| Development of an in vitro cell culture model to study milk to plasma ratios oftherapeutic drugs. | Indian J Pharmacol | 2013 Jul-Aug | 24014904 |
| Stability of extemporaneous pediatric oral liquids compounded from tablets anddrug substance: case of propranolol and theophylline. | Acta Pol Pharm | 2013 Jan-Feb | 23610969 |
| Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry. | Food Chem | 2013 Dec 1 | 23871018 |
| Application of organogels as oral controlled release formulations of hydrophilic drugs. | Int J Pharm | 2012 Oct 15 | 22766444 |
| Effects of quinoa hull meal on piglet performance and intestinal epithelialphysiology. | J Anim Physiol Anim Nutr (Berl) | 2012 Apr | 21392128 |
| Development of shellac-coated sustained release pellet formulations. | Eur J Pharm Sci | 2011 Mar 18 | 21251975 |
| Toxin-related seizures. | Emerg Med Clin North Am | 2011 Feb | 21109109 |
| Respiratory and cardiovascular effects of doxapram and theophylline for thetreatment of asphyxia in neonatal calves. | Theriogenology | 2010 Mar 15 | 20022095 |
| A G alpha subunit gene is essential for conidiation and potassium efflux butdispensable for pathogenicity of Alternaria alternata on citrus. | Curr Genet | 2010 Feb | 19949798 |
| Listeriolysin O affects barrier function and induces chloride secretion in HT-29/B6 colon epithelial cells. | Am J Physiol Gastrointest Liver Physiol | 2009 Jun | 19372105 |
| Intestinal physiology and peptidase activity in male pigs are modulated by consumption of corn culture extracts containing fumonisins. | J Nutr | 2009 Jul | 19474154 |
| Process analytical technology (PAT): effects of instrumental and compositionalvariables on terahertz spectral data quality to characterize pharmaceuticalmaterials and tablets. | Int J Pharm | 2007 Oct 1 | 17590292 |
Targets
- 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
References
- 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 ]
- 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
- 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 ]
- 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
- Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet. 2005 Jan 8-14;365(9454):167-75. [15639300 ]
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- 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
References
- 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 ]
- 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
References
- 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 ]
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- 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
- 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 ]
- 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
- 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 ]