Identification

Name
Sildenafil
Accession Number
DB00203  (APRD00556)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sildenafil is a vasoactive agent used to treat erectile dysfunction and reduce symptoms in patients with pulmonary arterial hypertension (PAH). Sildenafil elevates levels of the second messenger, cGMP, by inhibiting its breakdown via phosphodiesterase type 5 (PDE5). PDE5 is found in particularly high concentrations in the corpus cavernosum, erectile tissue of the penis. It is also found in the retina and vascular endothelium. Increased cGMP results in vasodilation which facilitates generation and maintenance of an erection. The vasodilatory effects of sildenafil also help reduce symptoms of PAH.

Structure
Thumb
Synonyms
  • 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine
External IDs
HIP-0908 / HIP0908
Product Ingredients
IngredientUNIICASInChI Key
Sildenafil citrateBW9B0ZE037171599-83-0DEIYFTQMQPDXOT-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act SildenafilTablet50 mgOralActavis Pharma Company2012-11-08Not applicableCanada
Act SildenafilTablet25 mgOralActavis Pharma Company2012-11-08Not applicableCanada
Act SildenafilTablet100 mgOralActavis Pharma Company2012-11-08Not applicableCanada
M-sildenafilTablet50 mgOralMantra Pharma IncNot applicableNot applicableCanada
M-sildenafilTablet100 mgOralMantra Pharma Inc2015-06-04Not applicableCanada
M-sildenafilTablet25 mgOralMantra Pharma IncNot applicableNot applicableCanada
Prz-sildenafilTablet100 mgOralPharmaris Canada IncNot applicableNot applicableCanada
RevatioInjection, solution0.8 mg/mlIntravenousPfizer Europe Ma Eeig2005-10-28Not applicableEu
RevatioInjection, solution0.8 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2009-11-18Not applicableUs
RevatioSolution0.8 mgIntravenousPfizer2010-08-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-sildenafilTablet25 mgOralApotex Corporation2012-11-14Not applicableCanada
Apo-sildenafilTablet100 mgOralApotex Corporation2012-11-09Not applicableCanada
Apo-sildenafilTablet50 mgOralApotex Corporation2012-11-14Not applicableCanada
Apo-sildenafil RTablet20 mgOralApotex Corporation2013-12-23Not applicableCanada
Auro-sildenafilTablet100 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-sildenafilTablet50 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-sildenafilTablet25 mgOralAuro Pharma IncNot applicableNot applicableCanada
Dom-sildenafilTablet100 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-sildenafilTablet50 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-sildenafilTablet25 mgOralDominion PharmacalNot applicableNot applicableCanada
Categories
UNII
3M7OB98Y7H
CAS number
139755-83-2
Weight
Average: 474.576
Monoisotopic: 474.204924168
Chemical Formula
C22H30N6O4S
InChI Key
BNRNXUUZRGQAQC-UHFFFAOYSA-N
InChI
InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)
IUPAC Name
5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one
SMILES
CCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC1

Pharmacology

Indication

For the treatment of erectile dysfunction and to relieve symptoms of pulmonary arterial hypertension (PAH).

Associated Conditions
Pharmacodynamics

Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Vasodilation results in high levels of blood flow causing the penis to grow to its full size. This stage is called tumescence. During the full-erection stage, blood flow fills penis sinusoids and outflow is restricted. This is followed by the rigid-erection phase during which the cavernous muscles contract causing the penis to become rigid. Little blood flow occurs during this stage. During the final stage, detumescence, the cavernous muscles relax and blood flows out of the penis. Erectile dysfunction may occur when there is insufficient blood supply to the penis or when the penis is unable to prevent outflow of blood from the penis. Sildenafil is a specific inhibitor of PDE5, an enzyme responsible for the breakdown of cGMP to 5’-GMP. Increased levels of cGMP stimulate vasodilation and facilitate the generation and maintenance of erections. These vasodilatory effects also help decrease symptoms of PAH. Sildenfail also exhibits some activity against PDE6 (10 times less potentcy compared to PDE5), a PDE isoform found predmoninantly in the retina. This activity is responsible for the blue tinged vision experienced by users of sildenafil.

Mechanism of action

Sildenafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by sildenafil enhances erectile function by increasing the amount of cGMP.

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Human
NRetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
Human
NRetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
Human
Absorption

>90% absorbed with ~40% reaching systemic circulation unchanged following first-pass metabolism

Volume of distribution
  • 105 L
Protein binding

96%

Metabolism

Sildenafil appears to be completely metabolized in the liver to 16 metabolites. Its metabolism is mediated mainly by cytochrome P450 microsomal isozymes 3A4 (major route) and 2C9 (minor route). The major circulating metabolite, N-demethylated metabolite, has PDE selectivity similar to the parent drug and ~50% of its in vitro potency. The N-demethylated metabolite is further metabolized to an N-dealkylated N,N-de-ethylated metabolite. Sildenafil also undergoes N-dealkylation followed by N-demethylation of the piperazine ring.

Route of elimination

Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).

Half life

4 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Angiotensin-converting enzyme---Not AvailableAlu insertions / Alu insertions  … show all Effect Directly StudiedPatients with this genotype have increased frequency of positive erectile response when using sildenafil to treat erectile dysfunctionDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3---(T;T)T allele, homozygoteEffect Directly StudiedPatients with this genotype have increased frequency of positive erectile response when using sildenafil to treat erectile dysfunctionDetails

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Sildenafil can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Sildenafil can be decreased when combined with (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of Sildenafil can be decreased when combined with 16-Bromoepiandrosterone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Sildenafil.
3,5-diiodothyropropionic acidThe metabolism of Sildenafil can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Sildenafil.
5-androstenedioneThe metabolism of Sildenafil can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Sildenafil can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Sildenafil can be decreased when combined with 6-O-benzylguanine.
AbemaciclibThe metabolism of Sildenafil can be decreased when combined with Abemaciclib.
Food Interactions
Not Available

References

Synthesis Reference

Peter James Dunn, Albert Shaw Wood, "Process for preparing sildenafil." U.S. Patent US5955611, issued December, 1994.

US5955611
General References
  1. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C: Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47-52. [PubMed:8858389]
  2. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM: ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Jan;33(1):273-82. [PubMed:9935041]
  3. Fries R, Shariat K, von Wilmowsky H, Bohm M: Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005 Nov 8;112(19):2980-5. [PubMed:16275885]
External Links
Human Metabolome Database
HMDB0005039
KEGG Drug
D08514
KEGG Compound
C07259
PubChem Compound
5212
PubChem Substance
46508371
ChemSpider
5023
BindingDB
14390
ChEBI
9139
ChEMBL
CHEMBL192
Therapeutic Targets Database
DAP000614
PharmGKB
PA451346
HET
VIA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Sildenafil
ATC Codes
G01AE10 — Combinations of sulfonamidesG04BE03 — Sildenafil
AHFS Codes
  • 24:12.12 — Phosphodiesterase Type 5 Inhibitors
PDB Entries
1tbf / 1udt / 1xos / 2h42 / 3jwq
FDA label
Download (80.5 KB)
MSDS
Download (37.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionImmersion Pulmonary Edema (IPE) / Swimming Induced Pulmonary Edema (SIPE)1
0CompletedTreatmentDermatomyositis / Lupus Erythematosus, Systemic / Raynaud Phenomenon Due to Trauma / Raynaud's Disease / System; Sclerosis / Ultrasound Therapy; Complications1
0Not Yet RecruitingTreatmentHemolysis / Thrombosis1
0RecruitingBasic ScienceMigraine With Aura1
0RecruitingOtherCongenital Heart Disease (CHD) / Liver Cirrhosis1
0RecruitingPreventionHand Foot Skin Reaction1
0TerminatedTreatmentErectile Dysfunction (ED) / Hypogonadism1
1CompletedNot AvailableErectile Dysfunction (ED)1
1CompletedNot AvailableFemale Sexual Health1
1CompletedNot AvailableNone Volunteer1
1CompletedBasic ScienceErectile Dysfunction (ED)4
1CompletedBasic ScienceErectile Dysfunction (ED) / Prostatic Hyperplasia / Urinary Bladder, Overactive1
1CompletedBasic ScienceGenetic Polymorphic CYP3A5 / Healthy Volunteers / Pharmacokinetics of Three PDE5Is1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedBasic SciencePersistent Pulmonary Hypertension of the Newborn1
1CompletedDiagnosticTraumatic Brain Injury (TBI)1
1CompletedOtherHealthy Volunteers1
1CompletedPreventionAcute Kidney Injury (AKI)1
1CompletedPreventionHealthy Volunteers1
1CompletedSupportive CareKidney Tumors1
1CompletedTreatmentCancer, Breast / Gastrointestinal Cancers / Genitourinary Cancers / Gynecologic Cancers / Sarcomas1
1CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
1CompletedTreatmentErectile Dysfunction (ED)2
1CompletedTreatmentHand Foot Syndrome / Palmar Plantar Erythrodysesthesia1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHeart Diseases1
1CompletedTreatmentHepatitis C Viral Infection1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentHypertension, Pulmonary [C08.381.423] / Pulmonary Hypertension (PH)1
1CompletedTreatmentPulmonary Arterial Hypertention1
1CompletedTreatmentSickle Cell Disorders1
1Not Yet RecruitingOtherErectile Dysfunction (ED)1
1RecruitingBasic ScienceMicrovascular coronary artery disease1
1RecruitingPreventionLabor Preterm Requiring Hospitalization1
1RecruitingTreatmentCerebral Vasospasm / Subarachnoid Hemorrhage1
1RecruitingTreatmentCombination of Oral Anticoagulation Therapy and Sildenafil / Intermediate-high Risk / Pulmonary Embolism (PE)1
1RecruitingTreatmentMild Traumatic Brain Injury (MTBI) / Post-Concussion Syndrome / Traumatic Brain Injury (TBI)1
1RecruitingTreatmentNeonatal Encephalopathy1
1RecruitingTreatmentTumors, Solid1
1RecruitingTreatmentUrinary Incontinence (UI)1
1TerminatedBasic ScienceCongestive Heart Failure (CHF) / Renal Dysfunction1
1TerminatedTreatmentLiver Cirrhosis1
1TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
1TerminatedTreatmentStroke, Ischemic1
1TerminatedTreatmentStrokes1
1WithdrawnSupportive CareCholangiocarcinomas / Malignant Neoplasm of Pancreas1
1, 2CompletedOtherBMI >30 kg/m2 / Metabolic Syndromes1
1, 2CompletedTreatmentCystic Fibrosis (CF)2
1, 2CompletedTreatmentDysmenorrhea1
1, 2CompletedTreatmentLymphangioma1
1, 2CompletedTreatmentNontuberculous Mycobacterial Infections1
1, 2CompletedTreatmentPulmonary Hypertension (PH)1
1, 2Enrolling by InvitationTreatmentHeart Failure, Unspecified / Renal Dysfunction1
1, 2RecruitingBasic ScienceEndothelial Dysfunction / Insulin Resistance1
1, 2RecruitingTreatmentMyelodysplastic Syndromes1
1, 2WithdrawnTreatmentCMRI of Lung Perfusion / Cystic Fibrosis With Mild to Moderate Lung Disease / Lung Perfusion / Lung Vascularization1
2Active Not RecruitingTreatmentCystic Fibrosis (CF)1
2Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2CompletedNot AvailableMild to Moderate Hypertension1
2CompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)1
2CompletedSupportive CareInfertilities1
2CompletedSupportive CareProstate Cancer1
2CompletedTreatmentActive Digital Ulcers1
2CompletedTreatmentAlveolitis, Fibrosing / Pulmonary Fibrosis / Pulmonary Hypertension (PH)1
2CompletedTreatmentBecker's Muscular Dystrophy (BMD)1
2CompletedTreatmentCystic Fibrosis (CF)1
2CompletedTreatmentEmphysema / Pulmonary Disease, Chronic Obstructive1
2CompletedTreatmentErectile Dysfunction (ED)4
2CompletedTreatmentFemale Sexual Arousal Disorder1
2CompletedTreatmentHeart Failure, Unspecified1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHypoactive Sexual Desire Disorder (HSDD)1
2CompletedTreatmentHypoplastic Left Heart Syndrome (HLHS) / Tricuspid Atresia1
2CompletedTreatmentNeonates and Preterm Infants1
2CompletedTreatmentPost-Concussive Syndrome / Traumatic Brain Injury (TBI)1
2CompletedTreatmentPulmonary Fibrosis / Pulmonary Hypertension (PH)1
2CompletedTreatmentPulmonary Hypertension (PH)3
2CompletedTreatmentSexual arousal disorders / Sexual Dysfunctions, Psychological1
2CompletedTreatmentSexual arousal disorders1
2CompletedTreatmentWaldenström's Macroglobulinemia (WM)1
2Enrolling by InvitationTreatmentBMI >30 kg/m21
2Enrolling by InvitationTreatmentPortopulmonary Hypertension1
2Not Yet RecruitingPreventionDiving / Edema, Pulmonary / Immersion1
2Not Yet RecruitingTreatmentInfants, Premature1
2Not Yet RecruitingTreatmentIntrauterine Growth Restriction1
2RecruitingPreventionAtherosclerosis / Rheumatoid Arthritis1
2RecruitingSupportive CareLymphatic Diseases / Lymphatic Malformations1
2RecruitingTreatmentBladder Cancers1
2RecruitingTreatmentBrain and Nervous System / Glioblastomas / Gliomas / Malignant Gliomas / Recurrent Adult Brain Neoplasm / WHO Grade III Glioma1
2RecruitingTreatmentChronic Lung Disease of Prematurity1
2RecruitingTreatmentConcussion, Brain / Post-Concussion Syndrome / Vascular System Injuries1
2TerminatedHealth Services ResearchAge-Related Macular Degeneration (ARMD)1
2TerminatedTreatmentBecker's Muscular Dystrophy (BMD) / Duchenne's Muscular Dystrophy (DMD)1
2TerminatedTreatmentParkinson's Disease (PD)1
2TerminatedTreatmentPersistent Pulmonary Hypertension / Respiratory Failure1
2TerminatedTreatmentPriapism / Sickle Cell Disorders1
2TerminatedTreatmentPulmonary Hypertension (PH)2
2TerminatedTreatmentPulmonary Hypertension (PH) / Sickle Cell Disorders1
2TerminatedTreatmentProphylaxis of preeclampsia1
2WithdrawnPreventionCerebral Vasospasm / Rupture of Intracranial Aneurysm / Subarachnoid Hemorrhage1
2WithdrawnPreventionCerebral Vasospasm / Subarachnoid Hemorrhage1
2WithdrawnTreatmentPersistent Pulmonary Hypertension of the Newborn1
2, 3Active Not RecruitingTreatmentDiseases of Mitral Valve / Pulmonary Hypertension (PH)1
2, 3CompletedTreatmentDiastolic Heart Failure / Pulmonary Hypertension (PH)1
2, 3CompletedTreatmentErectile Dysfunction (ED)1
2, 3CompletedTreatmentHeart Failure, Unspecified1
2, 3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Pulmonary Fibrosis1
2, 3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3CompletedTreatmentPulmonary Hypertension (PH) / Thalassaemic disorders1
2, 3CompletedTreatmentRaynaud's Phenomenon1
2, 3Not Yet RecruitingTreatmentPeripheral Arterial Disease (PAD)1
2, 3Not Yet RecruitingTreatmentPreterm Preeclampsia1
2, 3SuspendedTreatmentIntrauterine Growth Restriction (IUGR) / Intrauterine Growth Retardation1
2, 3TerminatedTreatmentIntrauterine Growth Retardation1
2, 3Unknown StatusTreatmentCardiovascular Disease (CVD) / Chronic Lung Diseases / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH) / Tanshinone IIA Sulfonate1
2, 3Unknown StatusTreatmentIntrauterine Growth Retardation1
3Active Not RecruitingTreatmentHeart Failure, Unspecified / Pulmonary Hypertension (PH)1
3CompletedPreventionErectile Dysfunction (ED) / Prostate Cancer1
3CompletedTreatmentChronic Lung Diseases1
3CompletedTreatmentCongestive Heart Failure (CHF)2
3CompletedTreatmentDiabetes Mellitus (DM)1
3CompletedTreatmentDiffuse Systemic Sclerosis / Raynaud's Phenomenon / Scleroderma, Limited / Scleroderma, Systemic1
3CompletedTreatmentEisenmenger's Syndrome1
3CompletedTreatmentEndothelial Dysfunction / Type 2 Diabetes Mellitus1
3CompletedTreatmentErectile Dysfunction (ED)2
3CompletedTreatmentHeart Failure, Diastolic / Pulmonary Hypertension (PH)1
3CompletedTreatmentHeart Failure, Unspecified3
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
3CompletedTreatmentIntrauterine Growth Retardation1
3CompletedTreatmentPeripheral Obliterative Arteriopathy1
3CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
3CompletedTreatmentPulmonary Arterial Hypertension, Children1
3CompletedTreatmentPulmonary Fibrosis / Pulmonary Hypertension (PH)1
3CompletedTreatmentPulmonary Hypertension (PH)4
3CompletedTreatmentScleroderma, Systemic1
3Not Yet RecruitingTreatmentPeripheral Artery Disease (PAD)1
3Not Yet RecruitingTreatmentPeripheral Obliterative Arteriopathy1
3RecruitingPreventionEnd Stage Heart Failure1
3RecruitingTreatmentErectile Dysfunction (ED) / Prostate Cancer1
3RecruitingTreatmentHeart Failure, Unspecified / Pulmonary Hypertension (PH)1
3RecruitingTreatmentPulmonary Hypertension (PH) / Systolic Dysfunction1
3RecruitingTreatmentPulmonary Hypertension, Familial Persistent, of the Newborn1
3SuspendedTreatmentHigh Blood Pressure (Hypertension)1
3TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
3TerminatedTreatmentPulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)2
3TerminatedTreatmentPulmonary Hypertension (PH)1
3Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
3Unknown StatusTreatmentErectile Dysfunction (ED)1
3Unknown StatusTreatmentPersistent Fetal Circulation Syndrome1
3WithdrawnNot AvailablePulmonary Hypertension (PH)1
3WithdrawnTreatmentArteriospasm coronary1
4Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4Active Not RecruitingTreatmentUreteral Stones / Urolithiasis1
4CompletedNot AvailableErectile Dysfunction (ED)3
4CompletedDiagnosticPulmonary Arterial Hypertension (PAH) / Ventricular Dysfunction, Left1
4CompletedEducational/Counseling/TrainingBlindness1
4CompletedPreventionHigh Altitude Pulmonary Edema / Other and unspecified effects of high altitude1
4CompletedTreatmentAngina Pectoris1
4CompletedTreatmentAortic Valve Stenosis1
4CompletedTreatmentArterial Hypertension / Erectile Dysfunction (ED)1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)2
4CompletedTreatmentDepression / Erectile Dysfunction (ED)1
4CompletedTreatmentDepression / Sexual Dysfunctions1
4CompletedTreatmentDiabetes Mellitus (DM) / Erectile Dysfunction (ED) / Testosterone Deficiency1
4CompletedTreatmentDiabetic Neuropathies1
4CompletedTreatmentEndometrial Preparation / Frozen Embryo Transfer1
4CompletedTreatmentEndothelial Dysfunction / Type 2 Diabetes Mellitus1
4CompletedTreatmentErectile Disfunction / Hemodialysis-dependent patients1
4CompletedTreatmentErectile Dysfunction (ED)20
4CompletedTreatmentErectile Dysfunction (ED) / High Blood Pressure (Hypertension)1
4CompletedTreatmentErectile Dysfunction (ED) / Parkinsons's Disease1
4CompletedTreatmentErectile Dysfunction (ED) / Spinal Cord Injuries (SCI) / Spinal Cord Trauma1
4CompletedTreatmentErectile Dysfunction (ED) / Type 2 Diabetes Mellitus1
4CompletedTreatmentHeart Failure, Diastolic1
4CompletedTreatmentHeart Failure, Unspecified / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
4CompletedTreatmentMeconium Aspiration Syndrome / Persistent Pulmonary Hypertension of Newborn (PPHN)1
4CompletedTreatmentMenière's Disease1
4CompletedTreatmentMitral Valve Surgery / Pulmonary Hypertension (PH)1
4CompletedTreatmentPediatric Pulmonary Hypertension1
4CompletedTreatmentPulmonary Arterial Hypertension (PAH)3
4CompletedTreatmentPulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1
4CompletedTreatmentPulmonary Hypertension (PH) / Valvular Heart Disease1
4CompletedTreatmentPulmonary Hypertension Associated With Connective Tissue Disease1
4CompletedTreatmentQuality of Life1
4CompletedTreatmentSafety1
4CompletedTreatmentSchizophrenic Disorders1
4No Longer AvailableNot AvailablePulmonary Arterial Hypertension (PAH)1
4Not Yet RecruitingBasic ScienceHealthy Volunteers1
4Not Yet RecruitingTreatmentInfertilities1
4Not Yet RecruitingTreatmentMyopathies1
4RecruitingBasic ScienceEmphysema2
4RecruitingTreatmentAssociated Pulmonary Arterial Hypertension1
4RecruitingTreatmentBMI >30 kg/m21
4RecruitingTreatmentIVF Failure1
4RecruitingTreatmentLife Change Events / Pulmonary Arterial Hypertension (PAH)1
4RecruitingTreatmentPulmonary Arterial Hypertension (PAH)2
4RecruitingTreatmentThalassaemic disorders1
4TerminatedTreatmentHeart Failure With Reactive Pulmonary Hypertension1
4TerminatedTreatmentHernia, Diaphragmatic / Hypoplasia, Pulmonary / Pulmonary Hypertension (PH)1
4TerminatedTreatmentProstatitis1
4TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
4Unknown StatusTreatmentCardiopulmonary Bypass1
4Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD) / Idiopathic Pulmonary Fibrosis (IPF)1
4Unknown StatusTreatmentErectile Dysfunction (ED)3
4Unknown StatusTreatmentErectile Dysfunction (ED) / Prostatic Neoplasms1
4Unknown StatusTreatmentFontan Circulation1
4Unknown StatusTreatmentHeart Failure, Unspecified1
4Unknown StatusTreatmentMyalgic Encephalomyelitis (ME)1
4Unknown StatusTreatmentPulmonary Arterial Hypertension (PAH)1
4Unknown StatusTreatmentPulmonary Hypertension Secondary to Lung Disease and/or Hypoxia1
4Unknown StatusTreatmentRecurrent Miscarriages1
4WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
4WithdrawnTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Interstitial Lung Disease (ILD) / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH)1
4WithdrawnTreatmentSickle Cell Disorders1
Not AvailableActive Not RecruitingTreatmentErectile Dysfunction (ED) / Penile Cancer / Radical Prostatectomy1
Not AvailableAvailableNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedNot AvailableAcute iron intoxication / Beta-Thalassemia / Bone destruction / Hematologic Diseases / Pulmonary Hypertension (PH) / Thalassaemic disorders / Thalassemia Major (TM)1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension) / Multiple System Atrophy (MSA) / Progressive autonomic failure1
Not AvailableCompletedNot AvailableProstate Cancer1
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)2
Not AvailableCompletedNot AvailablePulmonary Hypertension (PH)2
Not AvailableCompletedBasic ScienceAir Pollution / Exercise Performance / Pulmonary Artery Pressure / Pulmonary Hypertension (PH)1
Not AvailableCompletedDiagnosticCongenital Heart Disease (CHD)1
Not AvailableCompletedDiagnosticDiffuse Parenchymal Lung Diseases / Pulmonary Hypertension (PH)1
Not AvailableCompletedDiagnosticEndometrial Thickness1
Not AvailableCompletedHealth Services ResearchBMI >30 kg/m21
Not AvailableCompletedSupportive CareErectile Dysfunction (ED) / Prostate Cancer / Stage I Prostate Cancer / Stage II Prostate Cancer1
Not AvailableCompletedSupportive CareProstate Cancer / Psychosocial Effects of Cancer and Its Treatment / Radiation Toxicity / Sexual Dysfunctions / Sexuality and Reproductive Issues1
Not AvailableCompletedTreatmentAging / Tiredness1
Not AvailableCompletedTreatmentComplications, Pregnancy1
Not AvailableCompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentImprove Endothelial Function and Decrease Vascular Stenosis1
Not AvailableCompletedTreatmentNephrogenic Diabetes Insipidus1
Not AvailableCompletedTreatmentPulmonary Arterial Hypertension (PAH)1
Not AvailableCompletedTreatmentRecurrent Abortion1
Not AvailableCompletedTreatmentTiredness1
Not AvailableNo Longer AvailableNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableRecruitingNot AvailablePulmonary Arterial Hypertension (PAH)1
Not AvailableRecruitingNot AvailableTbi1
Not AvailableRecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
Not AvailableRecruitingTreatmentComplications, Pregnancy1
Not AvailableTerminatedNot AvailableCardiac Allograft Vasculopathy1
Not AvailableTerminatedSupportive CareErectile Dysfunction (ED) / Erectile Dysfunction Following Radical Prostatectomy / Erectile Dysfunction Following Simple Prostatectomy / Prostate Cancer1
Not AvailableUnknown StatusBasic ScienceCongenital Heart Disease (CHD)1
Not AvailableUnknown StatusDiagnosticErectile Dysfunction (ED)1
Not AvailableUnknown StatusEducational/Counseling/TrainingErectile Dysfunction (ED)1
Not AvailableUnknown StatusTreatmentProstate Cancer1
Not AvailableWithdrawnTreatmentPrimary and Secondary Pulmonary Hypertension1

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Pfizer ireland pharmaceuticals
Packagers
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Cardinal Health
  • Direct Dispensing Inc.
  • Diversified Healthcare Services Inc.
  • Gallipot
  • MSN Laboratories Ltd.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • US Pharmaceutical Group
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral25 mg
TabletOral100.0 mg
TabletOral25.0 mg
TabletOral50.0 mg
Injection, solutionIntravenous0.8 mg/ml
Injection, solutionIntravenous0.8 mg/1mL
Powder, for suspensionOral10 mg/1mL
Powder, for suspensionOral10 mg/ml
SolutionIntravenous0.8 mg
TabletOral20 mg
Tablet, film coatedOral20 mg
Injection, solutionIntravenous10 mg/12.5mL
TabletOral20 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral100 1/1
Tablet, film coatedOral100 mg
Tablet, film coatedOral25 mg
Tablet, film coatedOral50 mg
TabletOral50 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, orally disintegratingOral50 mg
Tablet, orally disintegratingOral100 mg
Tablet, orally disintegratingOral25 mg
Prices
Unit descriptionCostUnit
Sildenafil citrate powder24.38USD g
Viagra 50 mg tablet19.45USD tablet
Viagra 100 mg tablet19.45USD tablet
Viagra 25 mg tablet19.45USD tablet
Revatio 20 mg tablet17.5USD tablet
Revatio 10 mg/12.5 ml vial9.33USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5250534No1995-03-272012-03-27Us
CA2324324No2005-12-202020-10-26Canada
CA2044748No1998-02-032011-06-17Canada
US6469012Yes2000-04-222020-04-22Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189-190 °CNot Available
water solubility3.5 mg/mLNot Available
logP1.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.433 mg/mLALOGPS
logP2.35ALOGPS
logP1.65ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)7.27ChemAxon
pKa (Strongest Basic)5.97ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area109.13 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity139.44 m3·mol-1ChemAxon
Polarizability51.18 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6461
Caco-2 permeable+0.7078
P-glycoprotein substrateSubstrate0.7753
P-glycoprotein inhibitor IInhibitor0.672
P-glycoprotein inhibitor IIInhibitor0.8877
Renal organic cation transporterNon-inhibitor0.648
CYP450 2C9 substrateNon-substrate0.6553
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7254
CYP450 1A2 substrateNon-inhibitor0.823
CYP450 2C9 inhibitorInhibitor0.6864
CYP450 2D6 inhibitorNon-inhibitor0.8394
CYP450 2C19 inhibitorNon-inhibitor0.8222
CYP450 3A4 inhibitorInhibitor0.849
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5839
Ames testNon AMES toxic0.5683
CarcinogenicityNon-carcinogens0.6658
BiodegradationNot ready biodegradable0.7641
Rat acute toxicity2.6730 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8664
hERG inhibition (predictor II)Inhibitor0.7602
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0002900000-b281f59f40caaba85ac9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-4436900000-0c5804e76b9d495c76d6
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0459-6292000000-5a32bfcdda2067978be9
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0001900000-51b4957d0b3d25c41773
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01vk-0302900000-86c63c2fd17f7c5b7d6f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dj-8916100000-e941afc576d544ed32a7
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0059-2494500000-e3f8387aee5a0463363c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-05s0-3892000000-aa19715309275e16a6c0

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Pyrazolopyrimidines / Benzenesulfonyl compounds / Phenoxy compounds / Phenol ethers / Pyrimidones / Alkyl aryl ethers / N-methylpiperazines / Organosulfonamides / Sulfonyls / Pyrazoles
show 7 more
Substituents
Benzenesulfonamide / Pyrazolopyrimidine / Benzenesulfonyl group / Phenoxy compound / Phenol ether / Alkyl aryl ether / Pyrimidone / N-methylpiperazine / N-alkylpiperazine / Piperazine
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, piperazines, pyrazolopyrimidine (CHEBI:9139)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da
References
  1. Carson CC: Long-term use of sildenafil. Expert Opin Pharmacother. 2003 Mar;4(3):397-405. [PubMed:12614192]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Corbin JD, Francis SH, Webb DJ: Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology. 2002 Sep;60(2 Suppl 2):4-11. [PubMed:12414329]
  4. Kruuse C, Thomsen LL, Birk S, Olesen J: Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 2003 Jan;126(Pt 1):241-7. [PubMed:12477710]
  5. Rybalkin SD, Rybalkina IG, Shimizu-Albergine M, Tang XB, Beavo JA: PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J. 2003 Feb 3;22(3):469-78. [PubMed:12554648]
  6. Wang H, Liu Y, Huai Q, Cai J, Zoraghi R, Francis SH, Corbin JD, Robinson H, Xin Z, Lin G, Ke H: Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. J Biol Chem. 2006 Jul 28;281(30):21469-79. Epub 2006 May 30. [PubMed:16735511]
  7. Wang H, Ye M, Robinson H, Francis SH, Ke H: Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. [PubMed:17959709]
  8. Wang J, Re J, Wang Z: [Mode of action of sildenafil]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1999 Dec;21(6):493-6. [PubMed:12567500]
  9. Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [PubMed:17979301]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6G
Uniprot ID
P18545
Uniprot Name
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9643.09 Da
References
  1. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG: Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol. 2006 Dec;50(6):1194-207; discussion 1207. Epub 2006 Jun 6. [PubMed:16815627]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6H
Uniprot ID
Q13956
Uniprot Name
Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9074.36 Da
References
  1. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG: Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol. 2006 Dec;50(6):1194-207; discussion 1207. Epub 2006 Jun 6. [PubMed:16815627]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [PubMed:18308836]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. [PubMed:11298070]
  5. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [PubMed:18308836]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. [PubMed:11298070]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  5. Sildenafil FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Warrington JS, Shader RI, von Moltke LL, Greenblatt DJ: In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos. 2000 Apr;28(4):392-7. [PubMed:10725306]
  4. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. [PubMed:11298070]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Warrington JS, Shader RI, von Moltke LL, Greenblatt DJ: In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos. 2000 Apr;28(4):392-7. [PubMed:10725306]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. List of drugs that may have potential CYP2E1 interactions [File]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [PubMed:12036927]
  2. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. [PubMed:12695538]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name
ABCC5
Uniprot ID
O15440
Uniprot Name
Multidrug resistance-associated protein 5
Molecular Weight
160658.8 Da
References
  1. Jedlitschky G, Burchell B, Keppler D: The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem. 2000 Sep 29;275(39):30069-74. [PubMed:10893247]
  2. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. [PubMed:12695538]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [PubMed:12527806]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Kalliokoski A, Niemi M: Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x. Epub 2009 Sep 25. [PubMed:19785645]

Drug created on June 13, 2005 07:24 / Updated on October 17, 2018 17:16