[CAS NO. 58-55-9] Theophylline
PRODUCTS SPECIFICATIONS [58-55-9]
DESCRIPTION [58-55-9]
Overview
| MDL | MFCD00079619 |
|---|---|
| Molecular Weight | 180.16 |
| Molecular Formula | C7H8N4O2 |
| SMILES | O=C(N1C)N(C)C2=C(N=CN2)C1=O |
4 Publications Citing Use of MCE
Summary
Theophylline (1,3-Dimethylxanthine) is a potent phosphodiesterase (PDE) inhibitor, adenosine receptor antagonist, and histone deacetylase (HDAC) activator. Theophylline (1,3-Dimethylxanthine) inhibits PDE3 activity to relax airway smooth muscle. Theophylline (1,3-Dimethylxanthine) has anti-inflammatory activity by increase IL-10 and inhibit NF-κB into the nucleus. Theophylline (1,3-Dimethylxanthine) induces apoptosis . Theophylline (1,3-Dimethylxanthine) can be used for asthma and chronic obstructive pulmonary disease (COPD) research [1] [2] [3] [4] [5] .
IC50 & Target
|
IL-10 |
IL-6 |
PDE3 |
Human Endogenous Metabolite |
In Vitro
Theophylline (1,3-Dimethylxanthine) (1-1000 µM) inhibits cAMP hydrolysis by PDE in homogenates of bronchial tissue to relax human bronchus and pulmonary arteries
[1]
.
Theophylline (1,3-Dimethylxanthine) (10 µg/mL; 24 h; eosinophils) induces apoptosis through a reduction in the antiapoptotic protein Bcl-2
[2]
.
Theophylline (1,3-Dimethylxanthine) (0-500 µM; 2 h; A549 cells) inhibits NF-κB activation, I kappa B alpha (I-κBα) degradation and decreases the level of IL-6 in a concentration-dependent manner
[3]
.
Theophylline (1,3-Dimethylxanthine) (0-1000 µM; 30 min; A549 cells) induces histone deacetylase activity to decrease inflammatory gene expression
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [3]
| Cell Line: | A549 cells |
| Concentration: | 0, 20, 100 and 500 µM |
| Incubation Time: | 2 hours |
| Result: | Decreased the expression of NF-κB p65 and I-κBα degradation in a concentration-dependent manner. |
Western Blot Analysis [2]
| Cell Line: | Eosinophils |
| Concentration: | 10 µg/mL |
| Incubation Time: | 24 hours |
| Result: | Decreased the expression of Bcl-2. |
In Vivo
Theophylline (1,3-Dimethylxanthine) (100 mg/kg; i.p.; daily, for 9 d; male Swiss mice) has anti-inflammatory activity in mice and increases IL-6 and IL-10 levels and inhibits TNF-α and NO [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male Swiss mice [1] |
| Dosage: | 100 mg/kg |
| Administration: | Intraperitoneal injection; daily, for 9 days |
| Result: | Increased IL-6 and IL-10 levels and inhibited TNF-α and NO. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00241631 | Imperial College London|Mitsubishi Tanabe Pharma Corporation|Medical Research Council |
COPD
|
April 2006 | Phase 2 |
| NCT04309877 | University of California, Los Angeles |
Depression
|
March 2023 | Early Phase 1 |
| NCT04551170 | Vanderbilt University Medical Center |
Pseudohypoparathyroidism|Albright Hereditary Osteodystrophy|Pseudohypoparathyroidism Type 1a
|
July 13, 2020 | Phase 2 |
| NCT00252863 | AstraZeneca |
Asthma
|
December 2004 | Phase 3 |
| NCT02080078 | AHS Cancer Control Alberta|Cross Cancer Institute |
Non-small Cell Lung Cancer|Advanced Solid Malignancies
|
September 2014 | Phase 1 |
| NCT01415518 | AstraZeneca |
Chronic Obstructive Pulmonary Disease (COPD)
|
September 1, 2011 | Phase 4 |
| NCT00119496 | University of Glasgow|GlaxoSmithKline|Chest, Heart and Stroke Association Scotland|Chief Scientist Office of the Scottish Government |
Asthma
|
July 2005 | Phase 2|Phase 3 |
| NCT02088502 | Isfahan University of Medical Sciences |
Contrast-Induced Nephropathy
|
September 2013 | Phase 2|Phase 3 |
| NCT01601132 | Takeda |
Healthy
|
May 2012 | Phase 4 |
| NCT02001935 | Zhujiang Hospital |
Chronic Obstructive Pulmonary Disease
|
September 2013 | Not Applicable |
| NCT01794780 | Novartis Pharmaceuticals|Novartis |
COPD
|
February 5, 2013 | Phase 4 |
| NCT00003808 | Eastern Cooperative Oncology Group|National Cancer Institute (NCI)|North Central Cancer Treatment Group |
Leukemia
|
May 1999 | Phase 2 |
| NCT00299858 | Ottawa Hospital Research Institute|Ontario Lung Association |
COPD
|
October 2006 | Phase 2|Phase 3 |
| NCT00779259 | Mutual Pharmaceutical Company, Inc. |
Pharmacokinetics
|
August 2007 | Phase 1 |
| NCT01769898 | The First Affiliated Hospital of Guangzhou Medical University |
Bronchiectasis
|
July 2013 | Phase 4 |
| NCT01263106 | Eli Lilly and Company |
Major Depressive Disorder
|
December 2010 | Phase 1 |
| NCT03984188 | University of Miami|National Heart, Lung, and Blood Institute (NHLBI) |
COPD|COPD Exacerbation|COPD Exacerbation Acute|Pollution Related Respiratory Disorder|Pollution; Exposure
|
February 23, 2021 | Phase 3 |
| NCT04269187 | Assiut University |
Diaphragmatic Dysfunction in Critically Ill Patients
|
April 2020 | Early Phase 1 |
| NCT02340520 | UConn Health |
COPD
|
December 2014 | Phase 3 |
| NCT03029429 | Vanderbilt University Medical Center|Harvard University |
Pseudohypoparathyroidism|Albright Hereditary Osteodystrophy
|
September 1, 2018 | Phase 2 |
| NCT01696214 | University of California, San Diego|National Heart, Lung, and Blood Institute (NHLBI) |
Asthma
|
October 2012 | Phase 4 |
| NCT00003684 | NCIC Clinical Trials Group|Canadian Cancer Trials Group |
Pulmonary Complications|Quality of Life|Unspecified Adult Solid Tumor, Protocol Specific
|
March 24, 1998 | Phase 3 |
| NCT04240821 | Ashley Shoemaker|Vanderbilt University Medical Center |
Pseudohypoparathyroidism|Pseudohypoparathyroidism Type 1a|Albright Hereditary Osteodystrophy
|
May 22, 2020 | Phase 2 |
| NCT03718403 | Massachusetts General Hospital |
PHP Ia|PHP IB|Php1C
|
November 11, 2019 | Phase 4 |
| NCT01132781 | University of East Anglia|Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK) |
Rhinosinusitis|Asthma|Allergic Rhinitis
|
May 2010 | Phase 2 |
| NCT03894189 | Beni-Suef University |
Weaning Failure
|
May 2019 | Not Applicable |
| NCT00634413 | Pulmagen Therapeutics |
Chronic Obstructive Pulmonary Disease
|
February 2008 | Phase 2 |
| NCT00000578 | National Heart, Lung, and Blood Institute (NHLBI)|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
Asthma|Lung Diseases
|
April 1994 | Phase 3 |
| NCT03990766 | Washington University School of Medicine |
Olfactory Disorder|Anosmia|Viral Infection|Theophylline Causing Adverse Effects in Therapeutic Use|Smell Disorder
|
May 15, 2019 | Phase 2 |
| NCT02643602 | Technical University of Munich |
Radiographic Contrast Agent Nephropathy
|
December 2005 | Not Applicable |
| NCT03803215 | Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella|Gruppo Italiano Multidisciplinare per lo Studio della Sincope |
Syncope
|
May 11, 2016 | |
| NCT00756418 | Organon and Co |
Asthma
|
June 1, 2003 | Phase 4 |
| NCT02479451 | Massachusetts General Hospital |
End Stage Renal Disease|Olfactory Disorders
|
October 2015 | Phase 2 |
| NCT00983905 | Mutual Pharmaceutical Company, Inc. |
Pharmacokinetics
|
August 2008 | Phase 1 |
| NCT03269318 | Brighton and Sussex University Hospitals NHS Trust |
Asthma
|
July 1, 2017 | Phase 4 |
| NCT04148846 | University of Sao Paulo General Hospital |
Headache, Post-Dural Puncture
|
September 20, 2019 | Not Applicable |
| NCT02023554 | Zhujiang Hospital |
Chronic Obstructive Pulmonary Disease|Asthma
|
December 2013 | Not Applicable |
| NCT00671151 | Hospital Universitari Son Dureta|Fondo de Investigación Sanitaria (FIS)|Sociedad Española de Neumología y Cirugía Torácica |
COPD
|
June 2005 | Not Applicable |
| NCT01293734 | Liaoning University of Traditional Chinese Medicine|Shenyang Huanggu District Central Hospital|Benxi City hospital of Chinese medicine|Anshan Central Hospital |
Bronchial Asthma
|
December 2008 | Phase 2 |
| NCT00492518 | Technical University of Munich |
Contrast Induced Nephropathy|Kidney Diseases|Renal Failure|Adverse Effects
|
February 2002 | Phase 4 |
| NCT01017939 | Janssen Research & Development, LLC |
Prostate Neoplasms
|
January 2010 | Phase 1 |
| NCT02261727 | The George Institute|National Health and Medical Research Council, Australia |
Chronic Obstructive Pulmonary Disease
|
June 2014 | Phase 4 |
| NCT03015090 | XiaoGuang Zou|Southern Medical University, China|Kashgar 1st People´s Hospital |
Chronic Obstructive Pulmonary Disease
|
January 1, 2017 | Not Applicable |
| NCT01799161 | Eckhard Podack|University of Miami |
Non-Small Cell Lung Cancer|Non-small-cell Lung Carcinoma|Lung Cancer|NSCLC
|
December 2014 | Phase 1 |
| NCT00157937 | Organon and Co |
Asthma|Allergic Rhinitis
|
February 2003 | Phase 4 |
| NCT02463409 | Vanderbilt University Medical Center|Massachusetts General Hospital |
Pseudohypoparathyroidism Type 1a|Albright Hereditary Osteodystrophy
|
June 2015 | Phase 2 |
| NCT00252785 | AstraZeneca |
Asthma
|
October 2005 | Phase 3 |
| NCT02537691 | Hoffmann-La Roche |
Asthma
|
August 28, 2015 | Phase 4 |
| NCT01566565 | Norwegian Armed Forces Medical Service|Duke University|Oslo University Hospital |
High Altitude Pulmonary Hypertension
|
March 2012 | Phase 1 |
| NCT04789499 | Washington University School of Medicine |
Covid19|Anosmia|Olfactory Disorder|Covid-19 Pandemic|SARS-CoV-2 Infection|Hyposmia|Ageusia|Hypogeusia
|
March 15, 2021 | Phase 2 |
| NCT03115294 | Tampere University Hospital|Tampere University of Technology |
Heart Ventricles
|
May 16, 2016 | Not Applicable |
| NCT01066728 | University of Manitoba|Canadian Institutes of Health Research (CIHR)|The Children´s Hospital Foundation of Manitoba |
Apnea of Prematurity
|
August 2001 | Phase 2|Phase 3 |
| NCT04257851 | Damanhour Teaching Hospital |
Post-Dural Puncture Headache
|
February 15, 2020 | Phase 4 |
| NCT01684683 | The First Affiliated Hospital of Guangzhou Medical University |
Bronchiectasis
|
November 2012 | Phase 4 |
| NCT02273440 | Boehringer Ingelheim |
Healthy
|
May 2000 | Phase 1 |
| NCT01902758 | University of Montana |
Acute Mountain Sickness
|
August 2013 | Phase 2|Phase 3 |
| NCT00893009 | Assaf-Harofeh Medical Center |
COPD
|
July 2009 | Not Applicable |
| NCT01759862 | Stanford University |
Function of Renal Transplant
|
November 2012 | Not Applicable |
| NCT01599871 | Hospital Son Espases|Spanish Research Center for Respiratory Diseases|Fundación Mutua Madrileña |
Chronic Obstructive Pulmonary Disease
|
January 2011 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 11.11 mg/mL ( 61.67 mM ; Need ultrasonic)
H 2 O : 5 mg/mL ( 27.75 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 5.5506 mL | 27.7531 mL | 55.5062 mL |
| 5 mM | 1.1101 mL | 5.5506 mL | 11.1012 mL |
| 10 mM | 0.5551 mL | 2.7753 mL | 5.5506 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 11 mg/mL (61.06 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 1.11 mg/mL (6.16 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.11 mg/mL (6.16 mM); Clear solution
References
- [1] Rabe KF, et, al. Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J. 1995 Apr;8(4):637-42.
- [2] Németh ZH, et, al. Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice. Shock. 1997 May;7(5):371-5.
- [3] Ichiyama T, et, al. Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells. Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):558-61.
- [4] Ito K, et, al, 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.
- [5] Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013 Oct 15;188(8):901-6.
Synonyms
