Drugbank Logo

Showing drug card for Tadalafil (DB00820)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:16
Primary Accession Number DB00820
Secondary Accession Number
  • APRD00071
Name Tadalafil
Drug Type
  • Approved
  • Investigational
  • Small Molecule
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]
Synonyms
  1. CIA
  2. ICOS 351
  3. Tadanafil
  4. tadalafil
Brand Names
  1. Cialis
  2. Cialis/Tadalafil Hcl
  3. Cialis/Taladafil
Brand Mixtures Not Available
Chemical IUPAC Name (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
Chemical Formula C22H19N3O4
Chemical Structure Structure
CAS Registry Number 171596-29-5
InChI Identifier InChI=1/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
InChI Key WOXKDUGGOYFFRN-IIBYNOLFBU
KEGG Drug D02008 Link Image
KEGG Compound Not Available
PubChem Compound 110635 Link Image
PubChem Substance 687903 Link Image
ChEBI ID Not Available
PharmGKB ID PA10333 Link Image
HET ID CIA Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02248088 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/cialis.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cia1687.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Tadalafil Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 389.4040
Monoisotopic Molecular Weight 389.1376
State Solid
Melting Point 301-302 oC
Experimental Water Solubility Practically insoluble in water Source: PhysProp
Predicted Water Solubility 2.50e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.7 Source: PhysProp
Predicted LogP 2.36 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.19 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CN1CC(=O)N2[C@H](CC3=C(NC4=CC=CC=C34)[C@H]2C2=CC3=C(OCO3)C=C2)C1=O
Canonical SMILES CN1CC(=O)N2C(CC3=C(NC4=CC=CC=C34)C2C2=CC3=C(OCO3)C=C2)C1=O
Drug Category
  • Phosphodiesterase Inhibitors
  • Vasoconstrictor Agents
ATC Codes
AHFS Codes
  • 24:12.12
Indication Used for the treatment of erectile dysfunction
Pharmacology 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.
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.
Toxicity Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity.
Protein Binding 94%
Biotransformation 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.
Half Life 17.5 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Alfuzosin Tadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
Amprenavir Amprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Atazanavir Atazanavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Clarithromycin Clarithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Conivaptan Conivaptan may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Darunavir Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Delavirdine Delavirdine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Doxazosin Tadalafil may enhance the hypotensive effect of Doxazosin. Monitor for hypotension during concomitant therapy.
Fosamprenavir Fosamprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Imatinib Imatinib may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Indinavir Indinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isoniazid Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isosorbide Dinitrate The vasodilatory effects of Isosorbide dinitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Isosorbide Mononitrate The vasodilatory effects of Isosobide mononitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Itraconazole Itraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Ketoconazole Ketoconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Lopinavir Lopinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Miconazole Miconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nefazodone Nefazodone may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nelfinavir Nelfinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nicardipine Nicardipine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nitroglycerin The vasodilatory effects of Nitroglycerin may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Phenoxybenzamine Tadalafil may enhance the hypotensive effect of Phenoxybenzamine. Monitor for hypotension during concomitant therapy.
Phentolamine Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Posaconazole Posaconzole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Prazosin Tadalafil may enhance the hypotensive effect of Prazosin. Monitor for hypotension during concomitant therapy.
Quinidine Quinidine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Rifampin Rifampin may reduce Tadalafil plasma concentrations and efficacy.
Ritonavir Ritonavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Saquinavir Saquinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamsulosin Tadalafil may enhance the hypotensive effect of Tamsulosin. Monitor for hypotension during concomitant therapy.
Telithromycin Telithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Terazosin Tadalafil may enhance the hypotensive effect of Terazosin. Monitor for hypotension during concomitant therapy.
Tipranavir Tipranavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Voriconazole Voriconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Food Interactions Not Available
Pathways Not Available
General References
  1. 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 Link Image]
  2. Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. [PubMed Link Image]
  3. Burnett AL: Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health. J Androl. 2007 Oct 17;. [PubMed Link Image]
  4. Drugs.com Link Image
  5. Wikipedia Link Image
  6. RxList Link Image
  7. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. cGMP-specific 3',5'-cyclic phosphodiesterase
  2. cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 204
Target 1 Name cGMP-specific 3',5'-cyclic phosphodiesterase
Target 1 Synonyms
  1. CGB-PDE
  2. EC 3.1.4.35
  3. cGMP-binding cGMP-specific phosphodiesterase
Target 1 Gene Name PDE5A
Target 1 Protein Sequence >cGMP-specific 3',5'-cyclic phosphodiesterase 
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSVPGTPTRKISASEFDRPLRPIVVKDSEG
TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI
SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL
NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE
KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS
FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME
PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK
VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL
QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL
SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV
NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI
LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE
LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF
PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
Target 1 Number of Residues 889
Target 1 Molecular Weight 100014
Target 1 Theoretical pI 6.00
Target 1 GO Classification
Function
hydrolase activity
hydrolase activity, acting on ester bonds
phosphoric ester hydrolase activity
phosphoric diester hydrolase activity
cyclic-nucleotide phosphodiesterase activity
3',5'-cyclic-nucleotide phosphodiesterase activity
catalytic activity
Process
cellular process
cell communication
signal transduction
Component
Not Available
Target 1 General Function Involved in catalytic activity
Target 1 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
Target 1 Pathways Not Available
Target 1 Reactions
  • guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 3420185 Link Image
Target 1 UniProtKB/Swiss-Prot ID O76074 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name PDE5A_HUMAN Link Image
Target 1 PDB ID 1T9R Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >2628 bp 
ATGGAGCGGGCCGGCCCCAGCTTCGGGCAGCAGCGACAGCAGCAGCAGCCCCAGCAGCAG
AAGCAGCAGCAGAGGGATCAGGACTCGGTCGAAGCATGGCTGGACGATCACTGGGACTTT
ACCTTCTCATACTTTGTTAGAAAAGCCACCAGAGAAATGGTCAATGCATGGTTTGCTGAG
AGAGTTCACACCATCCCTGTGTGCAAGGAAGGTATCAGAGGCCACACCGAATCTTGCTCT
TGTCCCTTGCAGCAGAGTCCTCGTGCAGATAACAGTGTCCCTGGAACACCAACCAGGAAA
ATCTCTGCCTCTGAATTTGACCGGCCTCTTAGACCCATTGTTGTCAAGGATTCTGAGGGA
ACTGTGAGCTTCCTCTCTGACTCAGAAAAGAAGGAACAGATGCCTCTAACCCCTCCAAGG
TTTGATCATGATGAAGGGGACCAGTGCTCAAGACTCTTGGAATTAGTGAAGGATATTTCT
AGTCATTTGGATGTCACAGCCTTATGTCACAAAATTTTCTTGCATATCCATGGACTGATA
TCTGCTGACCGCTATTCCCTGTTCCTTGTCTGTGAAGACAGCTCCAATGACAAGTTTCTT
ATCAGCCGCCTCTTTGATGTTGCTGAAGGTTCAACACTGGAAGAAGTTTCAAATAACTGT
ATCCGCTTAGAATGGAACAAAGGCATTGTGGGACATGTGGCAGCGCTTGGTGAGCCCTTG
AACATCAAAGATGCATATGAGGATCCTCGGTTCAATGCAGAAGTTGACCAAATTACAGGC
TACAAGACACAAAGCATTCTTTGTATGCCAATTAAGAATCATAGGGAAGAGGTTGTTGGT
GTAGCCCAGGCCATCAACAAGAAATCAGGAAACGGTGGGACATTTACTGAAAAAGATGAA
AAGGACTTTGCTGCTTATTTGGCATTTTGTGGTATTGTTCTTCATAATGCTCAGCTCTAT
GAGACTTCACTGCTGGAGAACAAGAGAAATCAGGTGCTGCTTGACCTTGCTAGTTTAATT
TTTGAAGAACAACAATCATTAGAAGTAATTTTGAAGAAAATAGCTGCCACTATTATCTCT
TTCATGCAAGTGCAGAAATGCACCATTTTCATAGTGGATGAAGATTGCTCCGATTCTTTT
TCTAGTGTGTTTCACATGGAGTGTGAGGAATTAGAAAAATCATCTGATACATTAACAAGG
GAACATGATGCAAACAAAATCAATTACATGTATGCTCAGTATGTCAAAAATACTATGGAA
CCACTTAATATCCCAGATGTCAGTAAGGATAAAAGATTTCCCTGGACAACTGAAAATACA
GGAAATGTAAACCAGCAGTGCATTAGAAGTTTGCTTTGTACACCTATAAAAAATGGAAAG
AAGAATAAAGTTATAGGGGTTTGCCAACTTGTTAATAAGATGGAGGAGAATACTGGCAAG
GTTAAGCCTTTCAACCGAAATGACGAACAGTTTCTGGAAGCTTTTGTCATCTTTTGTGGC
TTGGGGATCCAGAACACGCAGATGTATGAAGCAGTGGAGAGAGCCATGGCCAAGCAAATG
GTCACATTGGAGGTTCTGTCGTATCATGCTTCAGCAGCAGAGGAAGAAACAAGAGAGCTA
CAGTCGTTAGCGGCTGCTGTGGTGCCATCTGCCCAGACCCTTAAAATTACTGACTTTAGC
TTCAGTGACTTTGAGCTGTCTGATCTGGAAACAGCACTGTGTACAATTCGGATGTTTACT
GACCTCAACCTTGTGCAGAACTTCCAGATGAAACATGAGGTTCTTTGCAGATGGATTTTA
AGTGTTAAGAAGAATTATCGGAAGAATGTTGCCTATCATAATTGGAGACATGCCTTTAAT
ACAGCTCAGTGCATGTTTGCTGCTCTAAAAGCAGGCAAAATTCAGAACAAGCTGACTGAC
CTGGAGATACTTGCATTGCTGATTGCTGCACTAAGCCACGATTTGGATCACCGTGGTGTG
AATAACTCTTACATACAGCGAAGTGAACATCCACTTGCCCAGCTTTACTGCCATTCAATC
ATGGAACACCATCATTTTGACCAGTGCCTGATGATTCTTAATAGTCCAGGCAATCAGATT
CTCAGTGGCCTCTCCATTGAAGAATATAAGACCACGTTGAAAATAATCAAGCAAGCTATT
TTAGCTACAGACCTAGCACTGTACATTAAGAGGCGAGGAGAATTTTTTGAACTTATAAGA
AAAAATCAATTCAATTTGGAAGATCCTCATCAAAAGGAGTTGTTTTTGGCAATGCTGATG
ACAGCTTGTGATCTTTCTGCAATTACAAAACCCTGGCCTATTCAACAACGGATAGCAGAA
CTTGTAGCAACTGAATTTTTTGATCAAGGAGACAGAGAGAGAAAAGAACTCAACATAGAA
CCCACTGATCTAATGAACAGGGAGAAGAAAAACAAAATCCCAAGTATGCAAGTTGGGTTC
ATAGATGCCATCTGCTTGCAACTGTATGAGGCCCTGACCCACGTGTCAGAGGACTGTTTC
CCTTTGCTAGATGGCTGCAGAAAGAACAGGCAGAAATGGCAGGCCCTTGCAGAACAGCAG
GAGAAGATGCTGATTAATGGGGAAAGCGGCCAGGCCAAGCGGAACTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID PDE5A Link Image
Target 1 GenAtlas ID PDE5A Link Image
Target 1 HGNC ID HGNC:8784 Link Image
Target 1 Chromosome Location 4
Target 1 Locus 4q25-q27
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Zhou L, Thompson WJ, Potter DE: Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1745-52. [PubMed Link Image]
  2. Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. [PubMed Link Image]
  3. Stacey P, Rulten S, Dapling A, Phillips SC: Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). Biochem Biophys Res Commun. 1998 Jun 18;247(2):249-54. [PubMed Link Image]
  4. Loughney K, Hill TR, Florio VA, Uher L, Rosman GJ, Wolda SL, Jones BA, Howard ML, McAllister-Lucas LM, Sonnenburg WK, Francis SH, Corbin JD, Beavo JA, Ferguson K: Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. Gene. 1998 Aug 17;216(1):139-47. [PubMed Link Image]
  5. Yanaka N, Kotera J, Ohtsuka A, Akatsuka H, Imai Y, Michibata H, Fujishige K, Kawai E, Takebayashi S, Okumura K, Omori K: Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Eur J Biochem. 1998 Jul 15;255(2):391-9. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1971
Target 2 Name cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Target 2 Synonyms
  1. DPDE2
  2. EC 3.1.4.17
  3. PDE46
Target 2 Gene Name PDE4A
Target 2 Protein Sequence >cAMP-specific 3',5'-cyclic phosphodiesterase 4A 
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Target 2 Number of Residues 900
Target 2 Molecular Weight 98144
Target 2 Theoretical pI 4.87
Target 2 GO Classification
Function
hydrolase activity
hydrolase activity, acting on ester bonds
phosphoric ester hydrolase activity
phosphoric diester hydrolase activity
cyclic-nucleotide phosphodiesterase activity
3',5'-cyclic-nucleotide phosphodiesterase activity
catalytic activity
Process
cellular process
cell communication
signal transduction
Component
Not Available
Target 2 General Function Involved in cAMP phosphodiesterase activity
Target 2 Specific Function Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate
Target 2 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 2 Reactions
  • nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 347120 Link Image
Target 2 UniProtKB/Swiss-Prot ID P27815 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PDE4A_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Isoform 4:Membrane
  • peripheral membrane protein. Note=Isoform 4 has propensity for association with
Target 2 Gene Sequence >2661 bp 
ATGGAACCCCCGACCGTCCCCTCGGAAAGGAGCCTGTCTCTGTCACTGCCCGGGCCCCGG
GAGGGCCAGGCCACCCTGAAGCCTCCCCCGCAGCACCTGTGGCGGCAGCCTCGGACCCCC
ATCCGTATCCAGCAGCGCGGCTACTCCGACAGCGCGGAGCGCGCCGAGCGGGAGCGGCAG
CCGCACCGGCCCATAGAGCGCGCCGATGCCATGGACACCAGCGACCGGCCCGGCCTGCGC
ACGACCCGCATGTCCTGGCCCTCGTCCTTCCATGGCACTGGCACCGGCAGCGGCGGCGCG
GGCGGAGGCAGCAGCAGGCGCTTCGAGGCAGAGAATGGGCCGACACCATCTCCTGGCCGC
AGCCCCCTGGACTCGCAGGCGAGCCCAGGACTCGTGCTGCACGCCGGGGCGGCCACCAGC
CAGCGCCGGGAGTCCTTCCTGTACCGCTCAGACAGCGACTATGACATGTCACCCAAGACC
ATGTCCCGGAACTCATCGGTCACCAGCGAGGCGCACGCTGAAGACCTCATCGTAACACCA
TTTGCTCAGGTGCTGGCCAGCCTCCGGAGCGTCCGTAGCAACTTCTCACTCCTGACCAAT
GTGCCCGTTCCCAGTAACAAGCGGTCCCCGCTGGGCGGCCCCACCCCTGTCTGCAAGGCC
ACGCTGTCAGAAGAAACGTGTCAGCAGTTGGCCCGGGAGACTCTGGAGGAGCTGGACTGG
TGTCTGGAGCAGCTGGAGACCATGCAGACCTATCGCTCTGTCAGCGAGATGGCCTCGCAC
AAGTTCAAAAGGATGTTGAACCGTGAGCTCACACACCTGTCAGAAATGAGCAGGTCCGGA
AACCAGGTCTCAGAGTACATTTCCACAACATTCCTGGACAAACAGAATGAAGTGGAGATC
CCATCACCCACGATGAAGGAACGAGAAAAACAGCAAGCGCCGCGACCAAGACCCTCCCAG
CCGCCCCCGCCCCCTGTACCACACTTACAGCCCATGTCCCAAATCACAGGGTTGAAAAAG
TTGATGCATAGTAACAGCCTGAACAACTCTAACATTCCCCGATTTGGGGTGAAGACCGAT
CAAGAAGAGCTCCTGGCCCAAGAACTGGAGAACCTGAACAAGTGGGGCCTGAACATCTTT
TGCGTGTCGGATTACGCTGGAGGCCGCTCACTCACCTGCATCATGTACATGATATTCCAG
GAGCGGGACCTGCTGAAGAAATTCCGCATCCCGGTGGACACGATGGTGACATACATGCTG
ACGCTGGAGGATCACTACCACGCTGACGTGGCCTACCATAACAGCCTGCACGCAGCTGAC
GTGCTGCAGTCCACCCACGTACTGCTGGCCACGCCTGCACTAGATGCAGTGTTCACGGAC
CTGGAGATTCTCGCCGCCCTCTTCGCGGCTGCCATCCACGATGTGGATCACCCTGGGGTC
TCCAACCAGTTCCTCATCAACACCAATTCGGAGCTGGCGCTCATGTACAACGATGAGTCG
GTGCTCGAGAATCACCACCTGGCCGTGGGCTTCAAGCTGCTGCAGGAGGACAACTGCGAC
ATCTTCCAGAACCTCAGCAAGCGCCAGCGGCAGAGCCTACGCAAGATGGTCATCGACATG
GTGCTGGCCACGGACATGTCCAAGCACATGACCCTCCTGGCTGACCTGAAGACCATGGTG
GAGACCAAGAAAGTGACCAGCTCAGGGGTCCTCCTGCTAGATAACTACTCCGACCGCATC
CAGGTCCTCCGGAACATGGTGCACTGTGCCGACCTCAGCAACCCCACCAAGCCGCTGGAG
CTGTACCGCCAGTGGACAGACCGCATCATGGCCGAGTTCTTCCAGCAGGGTGACCGAGAG
CGCGAGCGTGGCATGGAAATCAGCCCCATGTGTGACAAGCACACTGCCTCCGTGGAGAAG
TCTCAGGTGGGTTTTATTGACTACATTGTGCACCCATTGTGGGAGACCTGGGCGGACCTT
GTCCACCCAGATGCCCAGGAGATCTTGGACACTTTGGAGGACAACCGGGACTGGTACTAC
AGCGCCATCCGGCAGAGCCCATCTCCGCCACCCGAGGAGGAGTCAAGGGGGCCAGGCCAC
CCACCCCTGCCTGACAAGTTCCAGTTTGAGCTGACGCTGGAGGAGGAAGAGGAGGAAGAA
ATATCAATGGCCCAGATACCGTGCACAGCCCAAGAGGCATTGACTGCGCAGGGATTGTCA
GGAGTCGAGGAAGCTCTGGATGCAACCATAGCCTGGGAGGCATCCCCGGCCCAGGAGTCG
TTGGAAGTTATGGCACAGGAAGCATCCCTGGAGGCCGAGCTGGAGGCAGTGTATTTGACA
CAGCAGGCACAGTCCACAGGCAGTGCACCTGTGGCTCCGGATGAGTTCTCGTCCCGGGAG
GAATTCGTGGTTGCTGTAAGCCACAGCAGCCCCTCTGCCCTGGCTCTTCAAAGCCCCCTT
CTCCCTGCTTGGAGGACCCTGTCTGTTTCAGAGCATGCCCCGGGCCTCCCGGGCCTCCCC
TCCACGGCGGCCGAGGTGGAGGCCCAACGAGAGCACCAGGCTGCCAAGAGGGCTTGCAGT
GCCTGCGCAGGGACATTTGGGGAGGACACATCCGCACTCCCAGCTCCTGGTGGCGGGGGG
TCAGGTGGAGACCCTACCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID PDE4A Link Image
Target 2 GenAtlas ID PDE4A Link Image
Target 2 HGNC ID HGNC:8780 Link Image
Target 2 Chromosome Location 19
Target 2 Locus 19p13.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, Davis RL, Torphy TJ, Balcarek JM: Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. Mol Cell Biol. 1990 Jun;10(6):2678-86. [PubMed Link Image]
  2. Horton YM, Sullivan M, Houslay MD: Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected] Biochem J. 1995 Jun 1;308 ( Pt 2):683-91. [PubMed Link Image]
  3. Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD: Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1). Cell Signal. 1994 Sep;6(7):793-812. [PubMed Link Image]
  4. Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K: A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. Mol Cell Biol. 1993 Oct;13(10):6558-71. [PubMed Link Image]
  5. Sullivan M, Rena G, Begg F, Gordon L, Olsen AS, Houslay MD: Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2. Biochem J. 1998 Aug 1;333 ( Pt 3):693-703. [PubMed Link Image]
Target 2 Drug References
  1. Eardley I, Cartledge J: Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. [PubMed Link Image]
  2. 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 Link Image]
  3. Rotella DP: Tadalafil Lilly ICOS. Curr Opin Investig Drugs. 2003 Jan;4(1):60-5. [PubMed Link Image]
  4. Roumeguere T, Sternon J, Schulman CC: [Erectile dysfunction and phosphodiesterase type 5 inhibitors] Rev Med Brux. 2003 Jun;24(3):169-75. [PubMed Link Image]
  5. Curran M, Keating G: Tadalafil. Drugs. 2003;63(20):2203-12; discussion 2213-4. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.