Identification

Name
Tadalafil
Accession Number
DB00820  (APRD00071)
Type
Small Molecule
Groups
Approved, Investigational
Description

Tadalafil is an orally adminstered drug used to treat male erectile dysfunction (impotence). It is marketed worldwide under the brand name Cialis. It is a phosphodiesterase 5 (PDE5) inhibitor. Tadalafil's distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours). This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the "weekend pill." This longer half-life also is the basis of current investigation for tadalafil's use in pulmonary arterial hypertension as a once-daily therapy. [Wikipedia]

Structure
Thumb
Synonyms
  • (6R-trans)-6-(1,3-Benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione
  • (6R,12AR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-(methylenedioxy)phenyl) pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione
  • 6-BENZO[1,3]dioxol-5-yl-2-methyl-2,3,6,7,12,12a-hexahydro-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
  • ICOS 351
  • Tadanafil
External IDs
IC-351 / IC351
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act TadalafilTablet5 mgOralActavis Pharma Company2016-07-12Not applicableCanada
Act TadalafilTablet20 mgOralActavis Pharma Company2016-07-12Not applicableCanada
Act TadalafilTablet2.5 mgOralActavis Pharma Company2016-07-12Not applicableCanada
Act TadalafilTablet10 mgOralActavis Pharma Company2016-07-12Not applicableCanada
AdcircaTablet20 mg/1OralAphena Pharma Solutions Tennessee, Inc.2009-05-22Not applicableUs
AdcircaTablet20 mgOralEli Lilly & Co. Ltd.2010-01-19Not applicableCanada
AdcircaTablet, film coated20 mgOralEli Lilly Nederland B.V.2008-10-01Not applicableEu
AdcircaTablet20 mg/1OralUnited Therapeutics2009-05-22Not applicableUs
AdcircaTablet, film coated20 mgOralEli Lilly Nederland B.V.2008-10-01Not applicableEu
AdcircaTablet20 mg/1OralAvera McKennan Hospital2015-10-28Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-tadalafilTablet10 mgOralApotex Corporation2016-07-12Not applicableCanada
Apo-tadalafilTablet5 mgOralApotex Corporation2016-07-12Not applicableCanada
Apo-tadalafilTablet20 mgOralApotex Corporation2016-07-12Not applicableCanada
Apo-tadalafilTablet2.5 mgOralApotex Corporation2016-07-12Not applicableCanada
Apo-tadalafil PahTablet20 mgOralApotex Corporation2015-10-15Not applicableCanada
Auro-tadalafilTablet5 mgOralAuro Pharma Inc2016-07-14Not applicableCanada
Auro-tadalafilTablet20 mgOralAuro Pharma Inc2016-07-14Not applicableCanada
Auro-tadalafilTablet2.5 mgOralAuro Pharma Inc2016-07-14Not applicableCanada
Auro-tadalafilTablet10 mgOralAuro Pharma Inc2016-07-14Not applicableCanada
Dom-tadalafilTablet5 mgOralDominion PharmacalNot applicableNot applicableCanada
International/Other Brands
Adcirca / Cialis
Categories
UNII
742SXX0ICT
CAS number
171596-29-5
Weight
Average: 389.404
Monoisotopic: 389.137556111
Chemical Formula
C22H19N3O4
InChI Key
WOXKDUGGOYFFRN-IIBYNOLFSA-N
InChI
InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21-/m1/s1
IUPAC Name
(2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0³,⁸.0¹¹,¹⁶]heptadeca-1(10),11,13,15-tetraene-4,7-dione
SMILES
[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C1

Pharmacology

Indication

Used for the treatment of erectile dysfunction.

Associated Conditions
Pharmacodynamics

Tadalafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Tadalafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with tadalafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, tadalafil should not cause an erection.

Mechanism of action

Tadalafil 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 tadalafil enhances erectile function by increasing the amount of cGMP.

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Human
UDual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
inhibitor
Human
Absorption

After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.

Volume of distribution
  • 63 L
Protein binding

94%

Metabolism

Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. In vitro data suggests the metabolites are not expected to be pharmacologically active at observed metabolite concentrations.

Route of elimination

Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Half life

17.5 hours

Clearance
  • oral cl=2.5 L/hr
Toxicity

Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Tadalafil can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Tadalafil can be decreased when combined with (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of Tadalafil can be decreased when combined with 16-Bromoepiandrosterone.
3,5-diiodothyropropionic acidThe metabolism of Tadalafil can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tadalafil.
5-androstenedioneThe metabolism of Tadalafil can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Tadalafil can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Tadalafil can be decreased when combined with 6-O-benzylguanine.
AbacavirTadalafil may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe metabolism of Tadalafil can be decreased when combined with Abemaciclib.
Food Interactions
Not Available

References

Synthesis Reference

Ben-Zion Dolitzky, Dov Diller, "Preparation of tadalafil intermediates." U.S. Patent US20060276652, issued December 07, 2006.

US20060276652
General References
  1. Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. [PubMed:17927481]
  2. Burnett AL: Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health. J Androl. 2008 Jan-Feb;29(1):3-14. Epub 2007 Oct 17. [PubMed:17942972]
  3. Guazzi M, Samaja M: The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem. 2007;14(20):2181-91. [PubMed:17691956]
External Links
Human Metabolome Database
HMDB0014958
KEGG Drug
D02008
PubChem Compound
110635
PubChem Substance
46507646
ChemSpider
99301
BindingDB
14777
ChEBI
71940
ChEMBL
CHEMBL779
Therapeutic Targets Database
DAP000615
PharmGKB
PA10333
HET
CIA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tadalafil
ATC Codes
G04BE08 — Tadalafil
AHFS Codes
  • 24:12.12 — Phosphodiesterase Type 5 Inhibitors
PDB Entries
1udu / 1xoz
FDA label
Download (287 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingBasic ScienceMuscular Dystrophy1
0RecruitingTreatmentLarynx / Lip, Oral Cavity and Pharynx1
1CompletedNot AvailableBenign Prostatic Hyperplasia (BPH)1
1CompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)2
1CompletedBasic ScienceHealthy Volunteers1
1CompletedOtherHealthy Volunteers1
1CompletedOtherLocally Advanced Pancreatic Adenocarcinoma1
1CompletedPreventionBenign Prostatic Hyperplasia (BPH)1
1CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Erectile Dysfunction (ED)1
1CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHealty Male Volunteers1
1CompletedTreatmentLocally Advanced Malignant Neoplasm1
1RecruitingOtherEndothelial Dysfunction / Smoking1
1RecruitingPreventionAbdominal Cancer1
1TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
1TerminatedTreatmentType 2 Diabetes Mellitus1
1Unknown StatusNot AvailableBenign Prostatic Hyperplasia (BPH) / Healthy Volunteers1
1Unknown StatusTreatmentUniventricular heart1
1, 2Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
1, 2CompletedPreventionCongestive Heart Failure (CHF)1
1, 2RecruitingBasic ScienceImpaired Renal Function / Prophylaxis of cardiomyopathy2
1, 2RecruitingTreatmentHead and Neck Carcinoma / Head and Neck Squamous Cell Carcinoma (HNSCC)1
2Active Not RecruitingPreventionDementia, Vascular1
2Active Not RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
2CompletedTreatmentBenign Prostatic Hyperplasia (BPH)3
2CompletedTreatmentCerebral Small Vessels Disease / Stroke, Lacunar1
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
2CompletedTreatmentEisenmenger's Syndrome1
2CompletedTreatmentErectile Dysfunction (ED)3
2CompletedTreatmentGastroparesis1
2CompletedTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHypertension,Essential1
2CompletedTreatmentProstate / Prostatic Hyperplasia1
2CompletedTreatmentSclerosis, Progressive Systemic1
2RecruitingSupportive CareType 2 Diabetes Mellitus1
2RecruitingTreatmentAcromegaly Cardiomyopathy1
2RecruitingTreatmentCushing's Syndrome Cardiomyopathy1
2RecruitingTreatmentHealthy Volunteers / Obese1
2TerminatedTreatmentMultiple Myeloma (MM)1
2Unknown StatusTreatmentErectile Dysfunction (ED)1
2Unknown StatusTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2WithdrawnPreventionPriapism / Pulmonary Hypertension (PH) / Sickle Cell Disorders1
2, 3CompletedTreatmentBenign Prostatic Hyperplasia (BPH)1
2, 3CompletedTreatmentPulmonary Hypertension (PH)1
3CompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)1
3CompletedSupportive CareProstate Cancer / Sexual Dysfunctions1
3CompletedTreatmentBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Glucose tolerance impaired / Insulin Resistance1
3CompletedTreatmentBenign Prostatic Hyperplasia (BPH)6
3CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Enlarged Prostate1
3CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Erectile Dysfunction (ED)1
3CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Erectile Dysfunction (ED) / Prostatic Hyperplasia1
3CompletedTreatmentDigital Ulcers / Raynaud's Phenomenon / Scleroderma1
3CompletedTreatmentErectile Dysfunction (ED)11
3CompletedTreatmentErectile Dysfunction (ED) / Prostate Cancer1
3CompletedTreatmentErectile Dysfunction (ED) / Spinal Cord Injuries (SCI)1
3CompletedTreatmentLung Diseases, Interstitial1
3CompletedTreatmentPulmonary Hypertension (PH)3
3CompletedTreatmentRaynaud's Disease1
3RecruitingSupportive CareHeart Defects,Congenital / Transposition of Great Vessels With Ventricular Inversion1
3RecruitingTreatmentBenign Prostatic Hyperplasia (BPH) / Erectile Dysfunction (ED)1
3RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
3RecruitingTreatmentPulmonary Hypertension (PH)1
3TerminatedPreventionErectile Dysfunction (ED) / Prostate Cancer1
3TerminatedTreatmentHeart Failure, Unspecified / Pulmonary Hypertension (PH)1
3TerminatedTreatmentMuscular Dystrophy, Duchenne1
3WithdrawnPreventionHeart Failure, Unspecified / Pulmonary Hypertension (PH)1
4Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)2
4CompletedNot AvailableErectile Dysfunction (ED)1
4CompletedBasic ScienceBecker's Muscular Dystrophy (BMD)1
4CompletedTreatmentArterial Hypotension / Spinal Cord Injuries (SCI)1
4CompletedTreatmentBMI >30 kg/m21
4CompletedTreatmentBMI >30 kg/m2 / Sexual Dysfunctions1
4CompletedTreatmentBecker's Muscular Dystrophy (BMD)1
4CompletedTreatmentBenign Prostatic Hyperplasia (BPH)1
4CompletedTreatmentErectile Dysfunction (ED)13
4CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
4Enrolling by InvitationTreatmentCalcium Nephrolithiasis1
4RecruitingSupportive CareAndropause / Erectile Dysfunction (ED)1
4RecruitingTreatmentAortic Valve Stenosis / LV Remodeling, Hypertrophy1
4RecruitingTreatmentDiabetic Cardiomyopathy / Left Ventricular Hypertrophy / Type 2 Diabetes Mellitus1
4RecruitingTreatmentErectile Dysfunction (ED) / Parkinson's Disease (PD)1
4RecruitingTreatmentLiver Cirrhosis / Portopulmonary Hypertension / Pulmonary Hypertension (PH)1
4RecruitingTreatmentLower Urinary Tract Symptoms (LUTS) / Prostatic Hyperplasia1
4RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4TerminatedTreatmentAortic Valve Stenosis1
4TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1
4Unknown StatusTreatmentConnective Tissue Diseases / Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH) / Scleroderma Spectrum of Diseases / Sclerosis, Progressive Systemic1
4Unknown StatusTreatmentErectile Dysfunction (ED)1
4Unknown StatusTreatmentPulmonary Arterial Hypertension (PAH)1
4Unknown StatusTreatmentPulmonary Hypertension (PH)1
4WithdrawnTreatmentDiabetic Gastroparesis / Gastroparesis / Nausea / Vomiting1
Not AvailableCompletedNot AvailablePulmonary Arterial Hypertension (PAH)2
Not AvailableCompletedBasic ScienceMetabolic Syndromes1
Not AvailableCompletedPreventionEdema of the cerebrum / Pulmonary Edemas1
Not AvailableCompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
Not AvailableCompletedTreatmentHead and Neck Carcinoma1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentRaynaud's Disease1
Not AvailableCompletedTreatmentTiredness1
Not AvailableNot Yet RecruitingTreatmentLiver Cirrhosis1
Not AvailableUnknown StatusDiagnosticErectile Dysfunction (ED)1
Not AvailableWithdrawnTreatmentBecker's Muscular Dystrophy (BMD)1
Not AvailableWithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD)1

Pharmacoeconomics

Manufacturers
  • Eli lilly co
  • Eli lilly and co
  • Eli Lilly and Company
Packagers
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Diversified Healthcare Services Inc.
  • Eli Lilly & Co.
  • Lake Erie Medical and Surgical Supply
  • Lilly Del Caribe Inc.
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Southwood Pharmaceuticals
  • United Therapeutics Corp.
Dosage forms
FormRouteStrength
TabletOral20 mg/1
Tablet, film coatedOral20 mg
TabletOral10 mg
TabletOral2.5 mg
TabletOral20 mg
TabletOral5.0 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral10 mg
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral2.5 mg
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Cialis 30 5 mg tablet Box140.77USD box
Cialis 10 mg tablet20.92USD tablet
Cialis 20 mg tablet20.92USD tablet
Cialis 2.5 mg tablet4.76USD tablet
Cialis 5 mg tablet4.76USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2379948No2008-03-252020-04-26Canada
CA2181377No2002-05-282015-01-19Canada
US6140329No1996-07-112016-07-11Us
US6821975Yes2001-05-192021-05-19Us
US6943166Yes2000-10-262020-10-26Us
US7182958Yes2000-10-262020-10-26Us
US5859006Yes1998-05-212018-05-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)301-302 °CNot Available
water solubilityPractically insoluble in waterNot Available
logP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.25 mg/mLALOGPS
logP2.36ALOGPS
logP1.64ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.17ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area74.87 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity104.08 m3·mol-1ChemAxon
Polarizability40.92 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9933
Blood Brain Barrier+0.7821
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.6581
P-glycoprotein inhibitor INon-inhibitor0.59
P-glycoprotein inhibitor IINon-inhibitor0.775
Renal organic cation transporterNon-inhibitor0.7165
CYP450 2C9 substrateNon-substrate0.8742
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.7447
CYP450 2C9 inhibitorInhibitor0.5566
CYP450 2D6 inhibitorNon-inhibitor0.6788
CYP450 2C19 inhibitorInhibitor0.6998
CYP450 3A4 inhibitorNon-inhibitor0.6981
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7235
Ames testNon AMES toxic0.6466
CarcinogenicityNon-carcinogens0.931
BiodegradationNot ready biodegradable0.8906
Rat acute toxicity2.6521 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.976
hERG inhibition (predictor II)Non-inhibitor0.8734
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-03di-0090000000-c52485d22b5893fc60a2
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-03di-0090000000-2f6ad2194cd2932b0761
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0i0r-0291000000-a4ae40141abccfc86710
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0j59-0290000000-86095fe2d98833db9d0b
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0uy0-0429200000-641774545afc89315134
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0uy0-0429200000-f223c860e93cceeeacd8
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0292000000-0563bdd5b0be8c1cfa47
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02t9-2890000000-0be3708ad44a8a467cc5

Taxonomy

Description
This compound belongs to the class of organic compounds known as beta carbolines. These are compounds containing a 9H-pyrido[3,4-b]indole moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Pyridoindoles
Direct Parent
Beta carbolines
Alternative Parents
3-alkylindoles / Alpha amino acids and derivatives / Benzodioxoles / 2,5-dioxopiperazines / N-methylpiperazines / Benzenoids / Tertiary carboxylic acid amides / Pyrroles / Heteroaromatic compounds / Lactams
show 8 more
Substituents
Beta-carboline / Alpha-amino acid or derivatives / 3-alkylindole / Benzodioxole / Indole / 2,5-dioxopiperazine / Dioxopiperazine / N-methylpiperazine / N-alkylpiperazine / Benzenoid
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzodioxoles, pyrazinopyridoindole (CHEBI:71940)

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Curran M, Keating G: Tadalafil. Drugs. 2003;63(20):2203-12; discussion 2213-4. [PubMed:14498756]
  3. Eardley I, Cartledge J: Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. [PubMed:12074215]
  4. Montorsi F, Salonia A, Deho' F, Cestari A, Guazzoni G, Rigatti P, Stief C: Pharmacological management of erectile dysfunction. BJU Int. 2003 Mar;91(5):446-54. [PubMed:12603396]
  5. Rotella DP: Tadalafil Lilly ICOS. Curr Opin Investig Drugs. 2003 Jan;4(1):60-5. [PubMed:12625031]
  6. Roumeguere T, Sternon J, Schulman CC: [Erectile dysfunction and phosphodiesterase type 5 inhibitors]. Rev Med Brux. 2003 Jun;24(3):169-75. [PubMed:12891884]
  7. 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
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectiv...
Gene Name
PDE11A
Uniprot ID
Q9HCR9
Uniprot Name
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
Molecular Weight
104750.64 Da
References
  1. Weeks JL 2nd, Corbin JD, Francis SH: Interactions between cyclic nucleotide phosphodiesterase 11 catalytic site and substrates or tadalafil and role of a critical Gln-869 hydrogen bond. J Pharmacol Exp Ther. 2009 Oct;331(1):133-41. doi: 10.1124/jpet.109.156935. Epub 2009 Jul 29. [PubMed:19641165]
  2. Weeks JL 2nd, Zoraghi R, Francis SH, Corbin JD: N-Terminal domain of phosphodiesterase-11A4 (PDE11A4) decreases affinity of the catalytic site for substrates and tadalafil, and is involved in oligomerization. Biochemistry. 2007 Sep 11;46(36):10353-64. Epub 2007 Aug 16. [PubMed:17696499]

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. 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
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. Flockhart Table - Indiana University [Link]

Drug created on June 13, 2005 07:24 / Updated on October 15, 2018 04:36