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

Similar Structures

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

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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 Type	Indication	Combined Product Details	Approval Level	Dose Form
Treatment of	Benign prostate hyperplasia		••••••••••••
Used in combination to treat	Benign prostatic hyperplasia (bph)	Combination Product in combination with: Finasteride (DB01216)	••••••••••••	•••••••
Management of	Erectile dysfunction		••••••••••••
Management of	Pulmonary 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

Target	Actions	Organism
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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Tadalafil
- Tadalafil catechol metabolite
  - Tadalafil methylcatechol metabolite
    - Tadalafil methylcatechol glucuronide metabolite

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

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Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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.

Drug	Interaction
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Abacavir	Tadalafil may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abaloparatide	Abaloparatide may increase the hypotensive activities of Tadalafil.
Abametapir	The serum concentration of Tadalafil can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Tadalafil can be increased when combined with Abatacept.
Acalabrutinib	The 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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Act Tadalafil	Tablet	5 mg	Oral	TEVA Canada Limited	2016-07-12	Not applicable
Act Tadalafil	Tablet	20 mg	Oral	TEVA Canada Limited	2016-07-12	Not applicable
Act Tadalafil	Tablet	2.5 mg	Oral	TEVA Canada Limited	2016-07-12	Not applicable
Act Tadalafil	Tablet	10 mg	Oral	TEVA Canada Limited	2016-07-12	Not applicable
Adcirca	Tablet	20 mg/1	Oral	United Therapeutics Corporation	2009-05-22	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Ach-tadalafil	Tablet	20 mg	Oral	Accord Healthcare Inc	2023-03-30	Not applicable
Ach-tadalafil	Tablet	2.5 mg	Oral	Accord Healthcare Inc	Not applicable	Not applicable
Ach-tadalafil	Tablet	10 mg	Oral	Accord Healthcare Inc	2023-03-30	Not applicable
Ach-tadalafil	Tablet	5 mg	Oral	Accord Healthcare Inc	2023-03-30	Not applicable
Ag-tadalafil	Tablet	20 mg	Oral	Angita Pharma Inc.	2019-11-21	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Entadfi	Tadalafil (5 mg/1) + Finasteride (5 mg/1)	Capsule	Oral	Veru Inc.	2021-12-12	Not applicable
Opsynvi	Tadalafil (40 mg) + Macitentan (10 mg)	Tablet	Oral	Janssen Pharmaceuticals	2021-11-25	Not applicable
TADA PLUS 30/20 MG FILM KAPLI TABLET ,4 ADET	Tadalafil (20 mg) + Dapoxetine (30 mg)	Tablet, coated		NEUTEC İLAÇ SAN. TİC. A.Ş.	2014-09-11	Not applicable
TADA PLUS 30/20 MG FILM KAPLI TABLET ,8 ADET	Tadalafil (20 mg) + Dapoxetine (30 mg)	Tablet, coated		NEUTEC İLAÇ SAN. TİC. A.Ş.	2014-09-11	Not applicable

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

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]
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]
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]
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]
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]
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]
FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
DPD Approved Drug Products: Opsynvi (tadalafil/macitentan) combination tablets [Link]
Medisca: Tadalafil MSDS [Link]
FDA Approved Drug Products: Entadfi (finasteride/tadalafil) capsules for oral use [Link]

External Links

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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Benign Prostatic Hyperplasia (BPH) / Overactive Bladder Syndrome (OABS)	1
4	Active Not Recruiting	Treatment	Lower Ureteric Stones	1
4	Completed	Not Available	Sexual impotency	1
4	Completed	Basic Science	Becker's Muscular Dystrophy (BMD)	1
4	Completed	Diagnostic	Erectile Dysfunction / Erectile Dysfunction With Diabetes Mellitus	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

Form	Route	Strength
Film	Buccal	10.000 mg
Suspension	Oral	2 mg/mL
Granule	Oral	5.000 mg
Capsule	Oral	5.000 mg
Gel	Oral	20.000 mg
Film, soluble	Oral	5 mg
Tablet	Oral	5.000 mg
Tablet	Oral	10 mg
Tablet	Oral	2.5 mg
Tablet	Oral	20.000 mg
Tablet	Oral	5 mg
Tablet, film coated	Oral	10 mg/1
Tablet, film coated	Oral	2.5 mg/1
Tablet, film coated	Oral	20 mg/1
Tablet, film coated	Oral	5 mg/1
Tablet, coated	Oral	10 mg
Tablet, coated	Oral	5 mg
Tablet, coated	Oral
Film, soluble	Oral
Tablet	Oral	20.00 mg
Tablet, soluble	Oral	10 mg
Tablet, orally disintegrating	Oral
Capsule	Oral
Tablet, orally disintegrating	Oral	10 mg
Tablet, chewable	Oral	20 MG
Tablet	Oral	5.00 mg
Tablet, film coated	Oral
Tablet	Oral
Tablet, coated
Tablet, film coated	Oral	10.000 mg
Tablet, film coated	Oral	2.500 mg
Tablet, film coated	Oral	20.000 mg
Tablet, film coated	Oral	5.000 mg
Tablet	Oral	10 mg/1
Tablet	Oral	2.5 mg/1
Tablet	Oral	20 mg/1
Tablet	Oral	5 mg/1
Tablet, coated	Oral	10 mg/1
Tablet, coated	Oral	2.5 mg/1
Tablet, coated	Oral	20 mg/1
Tablet, coated	Oral	5 mg/1
Tablet	Oral
Tablet, film coated	Oral	2.5 MG
Capsule		10 mg
Capsule		20 mg
Capsule		5 mg
Tablet, orally disintegrating	Oral	20 mg
Tablet, soluble	Oral	5 mg
Tablet, soluble	Oral	500000 mg
Tablet, chewable	Oral	5 mg
Suspension	Oral	20 mg/5mL
Tablet, effervescent		10 mg
Tablet, effervescent
Tablet, effervescent		20 mg
Film, soluble	Oral	10 Mg
Film, soluble	Oral	20 Mg
Tablet	Oral	133.333 mg
Tablet, film coated	Oral	10 mg
Tablet, film coated	Oral	20 mg
Tablet, film coated	Oral	5 mg
Tablet	Oral	20 mg
Tablet, orally disintegrating	Oral	5 mg
Tablet, coated	Oral	20 mg
Tablet, coated	Oral	2000000 mg

Prices

Unit description	Cost	Unit
Cialis 30 5 mg tablet Box	140.77USD	box
Cialis 10 mg tablet	20.92USD	tablet
Cialis 20 mg tablet	20.92USD	tablet
Cialis 2.5 mg tablet	4.76USD	tablet
Cialis 5 mg tablet	4.76USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2379948	No	2008-03-25	2020-04-26
CA2181377	No	2002-05-28	2015-01-19
US6140329	No	2000-10-31	2016-07-11
US6821975	Yes	2004-11-23	2021-05-19
US6943166	Yes	2005-09-13	2020-10-26
US7182958	Yes	2007-02-27	2020-10-26
US5859006	Yes	1999-01-12	2018-05-21
US11382917	No	2018-12-24	2038-12-24
US11666576	No	2018-12-24	2038-12-24

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	301-302 °C	Medisca: Tadalafil MSDS
water solubility	Practically insoluble in water	Medisca: Tadalafil MSDS
logP	2.89	Medisca: Tadalafil MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.25 mg/mL	ALOGPS
logP	2.36	ALOGPS
logP	1.64	Chemaxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	15.17	Chemaxon
pKa (Strongest Basic)	-4.2	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	74.87 Å²	Chemaxon
Rotatable Bond Count	1	Chemaxon
Refractivity	104.08 m³·mol^-1	Chemaxon
Polarizability	40.92 Å³	Chemaxon
Number of Rings	6	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9933
Blood Brain Barrier	+	0.7821
Caco-2 permeable	+	0.5
P-glycoprotein substrate	Substrate	0.6581
P-glycoprotein inhibitor I	Non-inhibitor	0.59
P-glycoprotein inhibitor II	Non-inhibitor	0.775
Renal organic cation transporter	Non-inhibitor	0.7165
CYP450 2C9 substrate	Non-substrate	0.8742
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.7407
CYP450 1A2 substrate	Non-inhibitor	0.7447
CYP450 2C9 inhibitor	Inhibitor	0.5566
CYP450 2D6 inhibitor	Non-inhibitor	0.6788
CYP450 2C19 inhibitor	Inhibitor	0.6998
CYP450 3A4 inhibitor	Non-inhibitor	0.6981
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7235
Ames test	Non AMES toxic	0.6466
Carcinogenicity	Non-carcinogens	0.931
Biodegradation	Not ready biodegradable	0.8906
Rat acute toxicity	2.6521 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.976
hERG inhibition (predictor II)	Non-inhibitor	0.8734

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0006-3097000000-803ff86b2ce502e2bc83
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-02t9-2890000000-0be3708ad44a8a467cc5
MS/MS Spectrum - Linear Ion Trap , negative	LC-MS/MS	splash10-03di-0090000000-c52485d22b5893fc60a2
MS/MS Spectrum - Linear Ion Trap , negative	LC-MS/MS	splash10-03di-0090000000-2f6ad2194cd2932b0761
MS/MS Spectrum - Linear Ion Trap , positive	LC-MS/MS	splash10-0i0r-0291000000-a4ae40141abccfc86710
MS/MS Spectrum - Linear Ion Trap , positive	LC-MS/MS	splash10-0j59-0290000000-86095fe2d98833db9d0b
MS/MS Spectrum - Linear Ion Trap , positive	LC-MS/MS	splash10-0uy0-0429200000-641774545afc89315134
MS/MS Spectrum - Linear Ion Trap , positive	LC-MS/MS	splash10-0uy0-0429200000-f223c860e93cceeeacd8
MS/MS Spectrum - , positive	LC-MS/MS	splash10-014i-0292000000-0563bdd5b0be8c1cfa47
MS/MS Spectrum - , positive	LC-MS/MS	splash10-02t9-2890000000-0be3708ad44a8a467cc5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-0009000000-fac40b479b8719ddcf10
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000i-0009000000-2bfea16a9b34bf12e300
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-01ox-0029000000-a4bcb4f2924fd2251047
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03dr-0097000000-5e182f472b0efd7e614b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0cdr-2069000000-b5e53bce569a11384047
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0296-0039000000-5aa6c648eebf1173d0a9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-0009000000-fac40b479b8719ddcf10
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000i-0009000000-2bfea16a9b34bf12e300
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-01ox-0029000000-a4bcb4f2924fd2251047
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0296-0039000000-5aa6c648eebf1173d0a9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03dr-0097000000-5e182f472b0efd7e614b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0cdr-2069000000-b5e53bce569a11384047
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[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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Details1. cGMP-specific 3',5'-cyclic phosphodiesterase

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

Curran M, Keating G: Tadalafil. Drugs. 2003;63(20):2203-12; discussion 2213-4. [Article]
Eardley I, Cartledge J: Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. [Article]
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]
Rotella DP: Tadalafil Lilly ICOS. Curr Opin Investig Drugs. 2003 Jan;4(1):60-5. [Article]
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]
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]
FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	60000	N/A	N/A	A29072

Details2. Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A

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

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]
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]
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]
FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]

Details3. Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

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

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]
FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]

Enzymes

Details1. Cytochrome P450 3A4

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

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]
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]
FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
FDA Approved Drug Products: Adcirca (tadalafil) tablets [Link]
FDA Approved Drug Products: Cialis (tadalafil) tablets [Link]
Tadalafil FDA label [File]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Tadalafil

Identification

Structure for Tadalafil (DB00820)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

Enzymes

References