Tadalafil

Identification

Summary

Tadalafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension.

Brand Names
Adcirca, Alyq, Cialis, Entadfi, Tadliq
Generic Name
Tadalafil
DrugBank Accession Number
DB00820
Background

Tadalafil is a selective phosphodiesterase-5 inhibitor that is used in the treatment of erectile dysfunction (ED), pulmonary arterial hypertension (PAH), and benign prostatic hypertrophy.8,9 It was first approved in 2003 by the FDA for use in ED and later in 2009 for PAH. In contrast to other PDE5 inhibitors like sildenafil, tadalafil has greater selectivity for PDE5 and a longer half-life which has made it a more suitable option for chronic once-daily dosing in the treatment of PAH.2

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 389.404
Monoisotopic: 389.137556111
Chemical Formula
C22H19N3O4
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
  • Tadalafil
  • Tadalafilo
External IDs
  • GF 196960
  • IC-351
  • IC351
  • ICOS 351

Pharmacology

Indication

Tadalafil is indicated for the treatment of erectile dysfunction (ED) and either alone or in combination with finasteride for the treatment of benign prostatic hypertrophy (BPH).7,11 It is also indicated for the treatment of pulmonary arterial hypertension (PAH) both alone and in combination with macitentan or other endothelin-1 antagonists.8,9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofBenign prostate hyperplasia••••••••••••
Used in combination to treatBenign prostatic hyperplasia (bph)Combination Product in combination with: Finasteride (DB01216)•••••••••••••••••••
Management ofErectile dysfunction••••••••••••
Management ofPulmonary arterial hypertension••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Tadalafil exerts a therapeutic effect in ED by increasing sexual stimulation-dependant smooth muscle relaxation in the penis, allowing the corpus cavernosum to fill with blood to produce an erection.2,3 Smooth muscle relaxation in the pulmonary vasculature helps to produce vasodilation in PAH which reduces blood pressure in the pulmonary arteries.3 In BPH, tadalafil may contribute to decreased smooth muscle cell proliferation which may reduce the size of the prostate and relieve the anatomical obstruction which produces urinary symptoms of BPH.4 The decreased affinity of tadalafil for PDE6 compared to other PDE5 inhibitors may explain the reduced incidence of visual side effects.8,9,2

Mechanism of action

Tadalafil is a selective phosphodiesterase-5 (PDE5) inhibitor that produces several downstream effects with the most common therapeutic effect being smooth muscle relaxation. 7 Patients may experience ED due to a variety of causes including psychogenic, neurogenic, vasculogenic, iatrogenic, or endocrine. 6 These causes result in dysfunction of penile smooth muscle relaxation through either disrupted neuronal signaling or direct influence on smooth muscle cells. During sexual arousal, non-adrenergic non-cholinergic (NANC) neurons release nitric oxide (NO). Nitric oxide stimulates guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP).2,3 cGMP activates the cGMP-dependent kinase (PKG) in a signal cascade which activates K+ channels leading to inhibition of Ca2+ channels, inhibits platelet activation, and inhibits smooth muscle cell proliferation while inducing apoptosis. This signal cascade is attenuated by PDE5 which breaks the phosphodiester bond of cGMP, converting it to GMP. Inhibition of PDE5 by tadalafil increases signaling via the PKG cascade which supports penile smooth muscle relaxation during sexual arousal by decreasing Ca2+ entry into smooth muscle cells. This smooth muscle relaxation allows blood to fill the corpus cavernosum thereby producing an erection.

In PAH, blood pressure in the pulmonary arteries is raised due to a variety of mechanisms stemming from endothelial dysfunction.3 Decreased production of NO and prostacyclin reduce vasodilatory signaling while overproduction of endothelin-1 and thromboxane increase vasoconstriction. Inflammation, thromboses, and hypoxia later contribute to vascular remodeling which further reduces luminal size. The resultant increase in blood pressure reduces the capacity for gas exchange and increases afterload at the right ventricle, producing symptoms of dyspnea, fatigue, and dizziness as well as leading to right-sided heart failure. Tadalafil exerts its therapeutic effect in PAH through boosting NO-cGMP signaling to contribute to smooth muscle relaxation as with ED.

Lastly, tadalafil is used to treat BPH.7 BPH produces urinary dysfunction through hyperproliferation of the epithelial and smooth muscle layers of the prostate.4 The increased size of the prostate blocks urine flow through the urethra resulting in higher residual volumes due to incomplete emptying. Tadalafil does not appear to exert its benefit via smooth muscle relaxation of the prostate. It may instead exert its effect through a mix of increased oxygenation and decreased inflammation, which decreases tissue remodeling, and inhibition of cell proliferation through the cGMP cascade.

The decreased affinity for PDE6 compared to other PDE5 inhibitors may explain the decreased incidence of visual side effects as PDE6 is present in the eye and contributes to color vision.8,9,2

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Humans
NDual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
inhibitor
Humans
NRetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
Humans
Absorption

Tadalafil has a tmax of 0.5-6h with a median of 2h in healthy adults. 1,7 The tmax in adults with PAH is reported as 2-8h with a median of 4h.8 There does not appear to be a significant effect on absorption when tadalafil is taken with food.1

Volume of distribution

Tadalafil has a mean apparent volume of distribution of 63L in healthy adults.1,7 The mean apparent volume of distribution is reported as 77L in adults with PAH.8

Protein binding

Tadalafil is 94% bound to plasma proteins.1,7,8

Metabolism

Tadalafil undergoes hepatic metabolism via CYP3A4 to a catechol metabolite.1,5,7,8 This catechol metabolite undergoes subsequent methylation and glucuronidation with the methyl-glucuronide metabolite becoming the primary metabolite in circulation. None of the known metabolites are considered to be active.

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Route of elimination

Tadalafil is primarily eliminated via hepatic metabolism.1,7,8 These metabolites are mainly excreted in the feces (61%) and to a lesser extent in the urine (36%)

Half-life

The mean half-life of elimination of tadalafil is 15-17.5h in healthy adults.1,7,8 The mean half-life of elimination in adults with PAH is reported as 35h.8

Clearance

The mean apparent oral clearance of tadalafil is 2.5-3.4L/h in healthy adults.1,7,8 The mean apparent oral clearance in adults with PAH is reported as 3.5L/h

Adverse Effects
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Toxicity

Symptoms of overdose are expected to be similar to typical adverse effects which may include headache, dyspepsia, back pain, myalgia, nasopharyngitis, and dizziness.7,8 Standard supportive care is recommended. Hemodialysis is not expected to contribute significantly to tadalafil clearance.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTadalafil may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbaloparatideAbaloparatide may increase the hypotensive activities of Tadalafil.
AbametapirThe serum concentration of Tadalafil can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Tadalafil can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Tadalafil can be decreased when combined with Acalabrutinib.
Food Interactions
  • Avoid excessive or chronic alcohol consumption. Ingesting excess amounts of alcohol (more than four drinks in a short time) may potentiate the hypotension and dizziness caused by tadalafil.
  • Avoid grapefruit products. Tadalafil is metabolized by CYP3A4, and grapefruit products are CYP3A4 inhibitors; therefore, coadministration may increase serum levels of tadalafil and result in increased hypotension.
  • Take with or without food.

Products

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Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act TadalafilTablet10 mgOralTEVA Canada Limited2016-07-12Not applicableCanada flag
Act TadalafilTablet5 mgOralTEVA Canada Limited2016-07-12Not applicableCanada flag
Act TadalafilTablet20 mgOralTEVA Canada Limited2016-07-12Not applicableCanada flag
Act TadalafilTablet2.5 mgOralTEVA Canada Limited2016-07-12Not applicableCanada flag
AdcircaTablet, film coated20 mgOralEli Lilly Nederland B.V.2016-09-07Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-tadalafilTablet2.5 mgOralAccord Healthcare IncNot applicableNot applicableCanada flag
Ach-tadalafilTablet10 mgOralAccord Healthcare Inc2023-03-30Not applicableCanada flag
Ach-tadalafilTablet5 mgOralAccord Healthcare Inc2023-03-30Not applicableCanada flag
Ach-tadalafilTablet20 mgOralAccord Healthcare Inc2023-03-30Not applicableCanada flag
Ag-tadalafilTablet10 mgOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
EntadfiTadalafil (5 mg/1) + Finasteride (5 mg/1)CapsuleOralVeru Inc.2021-12-12Not applicableUS flag
OpsynviTadalafil (40 mg) + Macitentan (10 mg)TabletOralJanssen Pharmaceuticals2021-11-25Not applicableCanada flag
TADA PLUS 30/20 MG FILM KAPLI TABLET ,4 ADETTadalafil (20 mg) + Dapoxetine (30 mg)Tablet, coatedNEUTEC İLAÇ SAN. TİC. A.Ş.2014-09-11Not applicableTurkey flag
TADA PLUS 30/20 MG FILM KAPLI TABLET ,8 ADETTadalafil (20 mg) + Dapoxetine (30 mg)Tablet, coatedNEUTEC İLAÇ SAN. TİC. A.Ş.2014-09-11Not applicableTurkey flag

Categories

ATC Codes
G04BE08 — TadalafilC02KX52 — Ambrisentan and tadalafilG04CB51 — Finasteride and tadalafilG04CA54 — Tamsulosin and tadalafilC02KX54 — Macitentan and tadalafil
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,4-diazinane / 2,5-dioxopiperazine / 3-alkylindole / Acetal / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzodioxole / Beta-carboline
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzodioxoles, pyrazinopyridoindole (CHEBI:71940)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
742SXX0ICT
CAS number
171596-29-5
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[8.7.0.0^{3,8}.0^{11,16}]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

References

Synthesis Reference

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

US20060276652
General References
  1. Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, Mitchell MI: Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006 Mar;61(3):280-8. doi: 10.1111/j.1365-2125.2005.02553.x. [Article]
  2. Andersson KE: PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554-2565. doi: 10.1111/bph.14205. Epub 2018 Apr 25. [Article]
  3. Arif SA, Poon H: Tadalafil: a long-acting phosphodiesterase-5 inhibitor for the treatment of pulmonary arterial hypertension. Clin Ther. 2011 Aug;33(8):993-1004. doi: 10.1016/j.clinthera.2011.06.008. Epub 2011 Jul 16. [Article]
  4. Monica FZ, De Nucci G: Tadalafil for the treatment of benign prostatic hyperplasia. Expert Opin Pharmacother. 2019 Jun;20(8):929-937. doi: 10.1080/14656566.2019.1589452. Epub 2019 Mar 22. [Article]
  5. Dalvie D, Obach RS, Kang P, Prakash C, Loi CM, Hurst S, Nedderman A, Goulet L, Smith E, Bu HZ, Smith DA: Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem Res Toxicol. 2009 Feb;22(2):357-68. doi: 10.1021/tx8004357. [Article]
  6. Yafi FA, Jenkins L, Albersen M, Corona G, Isidori AM, Goldfarb S, Maggi M, Nelson CJ, Parish S, Salonia A, Tan R, Mulhall JP, Hellstrom WJ: Erectile dysfunction. Nat Rev Dis Primers. 2016 Feb 4;2:16003. doi: 10.1038/nrdp.2016.3. [Article]
  7. FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
  8. FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
  9. DPD Approved Drug Products: Opsynvi (tadalafil/macitentan) combination tablets [Link]
  10. Medisca: Tadalafil MSDS [Link]
  11. FDA Approved Drug Products: Entadfi (finasteride/tadalafil) capsules for oral use [Link]
Human Metabolome Database
HMDB0014958
KEGG Drug
D02008
PubChem Compound
110635
PubChem Substance
46507646
ChemSpider
99301
BindingDB
14777
RxNav
358263
ChEBI
71940
ChEMBL
CHEMBL779
ZINC
ZINC000003993855
Therapeutic Targets Database
DAP000615
PharmGKB
PA10333
PDBe Ligand
CIA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tadalafil
PDB Entries
1udu / 1xoz
FDA label
Download (287 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentBenign Prostatic Hyperplasia (BPH) / Overactive Bladder Syndrome (OABS)1
4Active Not RecruitingTreatmentLower Ureteric Stones1
4CompletedNot AvailableSexual impotency1
4CompletedBasic ScienceBecker's Muscular Dystrophy (BMD)1
4CompletedDiagnosticErectile Dysfunction / Erectile Dysfunction With Diabetes Mellitus1

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
FilmBuccal10.000 mg
SuspensionOral2 mg/mL
GranuleOral5.000 mg
CapsuleOral5.000 mg
GelOral20.000 mg
Film, solubleOral5 mg
TabletOral5.000 mg
TabletOral10 mg
TabletOral2.5 mg
TabletOral20.000 mg
TabletOral5 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral5 mg/1
Tablet, coatedOral10 mg
Tablet, coatedOral5 mg
Tablet, coatedOral
Film, solubleOral
TabletOral20.00 mg
Tablet, solubleOral10 mg
Tablet, orally disintegratingOral
CapsuleOral
Tablet, orally disintegratingOral10 mg
Tablet, chewableOral20 MG
TabletOral5.00 mg
Tablet, film coatedOral
TabletOral
Capsule10 mg
Capsule20 mg
Capsule5 mg
Tablet, coated
Tablet, film coatedOral10.000 mg
Tablet, film coatedOral2.500 mg
Tablet, film coatedOral20.000 mg
Tablet, film coatedOral5.000 mg
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral2.5 mg/1
Tablet, coatedOral20 mg/1
Tablet, coatedOral5 mg/1
TabletOral
Tablet, film coatedOral2.5 MG
Tablet, orally disintegratingOral20 mg
Tablet, solubleOral5 mg
Tablet, solubleOral500000 mg
Tablet, chewableOral5 mg
SuspensionOral20 mg/5mL
Tablet, effervescent10 mg
Tablet, effervescent
Tablet, effervescent20 mg
Film, solubleOral10 Mg
Film, solubleOral20 Mg
TabletOral133.333 mg
Tablet, film coatedOral10 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral5 mg
TabletOral20 mg
Tablet, orally disintegratingOral5 mg
Tablet, coatedOral20 mg
Tablet, coatedOral2000000 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)Region
CA2379948No2008-03-252020-04-26Canada flag
CA2181377No2002-05-282015-01-19Canada flag
US6140329No2000-10-312016-07-11US flag
US6821975Yes2004-11-232021-05-19US flag
US6943166Yes2005-09-132020-10-26US flag
US7182958Yes2007-02-272020-10-26US flag
US5859006Yes1999-01-122018-05-21US flag
US11382917No2018-12-242038-12-24US flag
US11666576No2018-12-242038-12-24US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)301-302 °CMedisca: Tadalafil MSDS
water solubilityPractically insoluble in waterMedisca: Tadalafil MSDS
logP2.89Medisca: Tadalafil MSDS
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-MSsplash10-0006-3097000000-803ff86b2ce502e2bc83
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-02t9-2890000000-0be3708ad44a8a467cc5
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-fac40b479b8719ddcf10
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0009000000-2bfea16a9b34bf12e300
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-0029000000-a4bcb4f2924fd2251047
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dr-0097000000-5e182f472b0efd7e614b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0cdr-2069000000-b5e53bce569a11384047
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0296-0039000000-5aa6c648eebf1173d0a9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-fac40b479b8719ddcf10
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0009000000-2bfea16a9b34bf12e300
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-0029000000-a4bcb4f2924fd2251047
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0296-0039000000-5aa6c648eebf1173d0a9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dr-0097000000-5e182f472b0efd7e614b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0cdr-2069000000-b5e53bce569a11384047
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-206.8616357
predicted
DarkChem Lite v0.1.0
[M-H]-206.5738357
predicted
DarkChem Lite v0.1.0
[M-H]-189.95772
predicted
DeepCCS 1.0 (2019)
[M-H]-206.8616357
predicted
DarkChem Lite v0.1.0
[M-H]-206.5738357
predicted
DarkChem Lite v0.1.0
[M-H]-189.95772
predicted
DeepCCS 1.0 (2019)
[M+H]+207.2695357
predicted
DarkChem Lite v0.1.0
[M+H]+206.7156357
predicted
DarkChem Lite v0.1.0
[M+H]+192.35329
predicted
DeepCCS 1.0 (2019)
[M+H]+207.2695357
predicted
DarkChem Lite v0.1.0
[M+H]+206.7156357
predicted
DarkChem Lite v0.1.0
[M+H]+192.35329
predicted
DeepCCS 1.0 (2019)
[M+Na]+206.6459357
predicted
DarkChem Lite v0.1.0
[M+Na]+198.26581
predicted
DeepCCS 1.0 (2019)
[M+Na]+206.6459357
predicted
DarkChem Lite v0.1.0
[M+Na]+198.26581
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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. Curran M, Keating G: Tadalafil. Drugs. 2003;63(20):2203-12; discussion 2213-4. [Article]
  2. Eardley I, Cartledge J: Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. [Article]
  3. 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. [Article]
  4. Rotella DP: Tadalafil Lilly ICOS. Curr Opin Investig Drugs. 2003 Jan;4(1):60-5. [Article]
  5. 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. [Article]
  6. Blount MA, Beasley A, Zoraghi R, Sekhar KR, Bessay EP, Francis SH, Corbin JD: Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004 Jul;66(1):144-52. doi: 10.1124/mol.66.1.144. [Article]
  7. FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
  8. FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. [Article]
  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. [Article]
  3. Andersson KE: PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554-2565. doi: 10.1111/bph.14205. Epub 2018 Apr 25. [Article]
  4. FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
  5. FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
Kind
Protein
Organism
Humans
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. Andersson KE: PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery. Br J Pharmacol. 2018 Jul;175(13):2554-2565. doi: 10.1111/bph.14205. Epub 2018 Apr 25. [Article]
  2. FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
  3. FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
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. Takahiro R, Nakamura S, Kohno H, Yoshimura N, Nakamura T, Ozawa S, Hirono K, Ichida F, Taguchi M: Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65. doi: 10.1248/bpb.b14-00566. [Article]
  2. Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, Mitchell MI: Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2006 Mar;61(3):280-8. doi: 10.1111/j.1365-2125.2005.02553.x. [Article]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
  5. FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
  6. Tadalafil FDA label [File]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48