Target Information
| Target General Information | Top | |||||
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| Target ID |
T07663
(Former ID: TTDS00296)
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| Target Name |
Phosphodiesterase 5A (PDE5A)
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| Synonyms |
cGMP-specific 3',5'-cyclic phosphodiesterase; PDE5A; CGMP-binding cGMP-specific phosphodiesterase; CGB-PDE
Click to Show/Hide
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| Gene Name |
PDE5A
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Hypertension [ICD-11: BA00-BA04] | |||||
| 2 | Innate/adaptive immunodeficiency [ICD-11: 4A00] | |||||
| 3 | Sexual dysfunction [ICD-11: HA00-HA01] | |||||
| 4 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
| 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. Specifically regulates nitric-oxide-generated cGMP.
Click to Show/Hide
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| BioChemical Class |
Phosphoric diester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.4.35
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| Sequence |
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T32BH6 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | Dipyridamole | Drug Info | Approved | Hypertension | [6], [7] | |
| 2 | Papaverine | Drug Info | Approved | Spasm | [8] | |
| 3 | Tadalafil | Drug Info | Approved | Erectile dysfunction | [9], [10] | |
| 4 | Udenafil | Drug Info | Approved | Erectile dysfunction | [11] | |
| 5 | Vardenafil | Drug Info | Approved | Erectile dysfunction | [10], [12] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | EXISULIND | Drug Info | Phase 3 | Colorectal cancer | [13] | |
| 2 | PF-489791 | Drug Info | Phase 2 | Raynaud disease | [14] | |
| 3 | UK-371800 | Drug Info | Phase 1 | Erectile dysfunction | [15] | |
| Discontinued Drug(s) | [+] 6 Discontinued Drugs | + | ||||
| 1 | BRL-61063 | Drug Info | Discontinued in Phase 2 | Allergy | [17] | |
| 2 | DASANTAFIL | Drug Info | Discontinued in Phase 2 | Erectile dysfunction | [18] | |
| 3 | E-4021 | Drug Info | Discontinued in Phase 2 | Cardiovascular disease | [19] | |
| 4 | SINITRODIL | Drug Info | Discontinued in Phase 2 | Angina pectoris | [20] | |
| 5 | SLX-2101 | Drug Info | Discontinued in Phase 2 | Raynaud disease | [21] | |
| 6 | UK-369003 | Drug Info | Discontinued in Phase 1/2 | Erectile dysfunction | [22], [23] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Dipyridamole | Drug Info | [26] | |||
| 2 | EXISULIND | Drug Info | [32] | |||
| 3 | SINITRODIL | Drug Info | [36] | |||
| 4 | RWJ-387273 | Drug Info | [49] | |||
| Inhibitor | [+] 29 Inhibitor drugs | + | ||||
| 1 | Papaverine | Drug Info | [27] | |||
| 2 | Tadalafil | Drug Info | [28], [29], [30] | |||
| 3 | Udenafil | Drug Info | [31] | |||
| 4 | ICARIIN | Drug Info | [33] | |||
| 5 | PF-489791 | Drug Info | [34] | |||
| 6 | UK-371800 | Drug Info | [15] | |||
| 7 | BRL-61063 | Drug Info | [35] | |||
| 8 | DASANTAFIL | Drug Info | [36] | |||
| 9 | E-4021 | Drug Info | [37] | |||
| 10 | SLX-2101 | Drug Info | [38] | |||
| 11 | UK-369003 | Drug Info | [39], [40] | |||
| 12 | IMAZODAN | Drug Info | [41] | |||
| 13 | Trequinsin | Drug Info | [42] | |||
| 14 | ZAPRINAST | Drug Info | [43] | |||
| 15 | 3,7-Bis(2-hydroxyethyl)icaritin | Drug Info | [33] | |||
| 16 | 7-(2-Hydroxyethyl)-3-O-rhamnosylicariin | Drug Info | [33] | |||
| 17 | Benzo[1,3]dioxol-5-ylmethyl-quinazolin-4-yl-amine | Drug Info | [44] | |||
| 18 | CKD-533 | Drug Info | [45] | |||
| 19 | Gamma-Glutamyl[S-(2-Iodobenzyl)Cysteinyl]Glycine | Drug Info | [46] | |||
| 20 | Guanosine-5'-Monophosphate | Drug Info | [46] | |||
| 21 | Icariside II | Drug Info | [33] | |||
| 22 | isobutylmethylxanthine | Drug Info | [47] | |||
| 23 | KURAIDIN | Drug Info | [48] | |||
| 24 | ROLIPRAM | Drug Info | [44] | |||
| 25 | SCH-57726 | Drug Info | [50] | |||
| 26 | SCH51866 | Drug Info | [51] | |||
| 27 | SOPHOFLAVESCENOL | Drug Info | [48] | |||
| 28 | SOPHORAFLAVANONE B | Drug Info | [33] | |||
| 29 | T0156 | Drug Info | [52] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Vardenafil | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Tadalafil | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Tadalafil | PDB:1XOZ | ||||
| Method | X-ray diffraction | Resolution | 1.37 Å | Mutation | Yes | [53] |
| PDB Sequence |
EEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHPGVSNQ663 FLINTNSELA673 LMYNDESVLE682 HHHFDQCLMI 692 LNSPGNQILS702 GLSIEEYKTT712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN 742 QFNLEDPHQK752 ELFLAMLMTA762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGDR 792 ERKELNIEPT802 DLMNREKKNK812 IPSMQVGFID822 AICLQLYEAL832 THVSEDCFPL 842 LDGCRKNRQK852 WQALAE
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Vardenafil | Ligand Info | |||||
| Structure Description | Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil | PDB:1XP0 | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | Yes | [53] |
| PDB Sequence |
EEETRELQSL
543 AAAVVPSAQT553 LKITDFSFSD563 FELSDLETAL573 CTIRMFTDLN583 LVQNFQMKHE 593 VLCRWILSVK603 KNYRKNVAYH613 NWRHAFNTAQ623 CMFAALKAGK633 IQNKLTDLEI 643 LALLIAALSH653 DLDHPGVSNQ663 FLINTNSELA673 LMYNDESVLE682 HHHFDQCLMI 692 LNSPGNQILS702 GLSIEEYKTT712 LKIIKQAILA722 TDLALYIKRR732 GEFFELIRKN 742 QFNLEDPHQK752 ELFLAMLMTA762 CDLSAITKPW772 PIQQRIAELV782 ATEFFDQGDR 792 ERKELNIEPT802 DLMNREKKNK812 IPSMQVGFID822 AICLQLYEAL832 THVSEDCFPL 842 LDGCRKNRQK852 WQALAE
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TYR612
3.717
HIS613
4.245
LEU725
4.056
ASP764
4.992
LEU765
3.863
ALA767
3.759
ILE768
3.806
GLN775
4.249
ILE778
4.639
ALA779
3.771
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| cGMP-PKG signaling pathway | hsa04022 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | cGMP-PKG signaling pathway | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TGF_beta_Receptor Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | cGMP effects | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol. 2002 Dec 4;40(11):2006-12. | |||||
| REF 2 | Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5. | |||||
| REF 3 | Recombinant human c1 inhibitor (conestat alfa): in the treatment of angioedema attacks in hereditary angioedema. BioDrugs. 2012 Oct 1;26(5):315-23. | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7448). | |||||
| REF 5 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
| REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4807). | |||||
| REF 7 | Inhibition of platelet activation and aggregation. Handb Exp Pharmacol. 2005;(170):443-62. | |||||
| REF 8 | Drug information of Papaverine, 2008. eduDrugs. | |||||
| REF 9 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7299). | |||||
| REF 10 | Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. | |||||
| REF 11 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 12 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7320). | |||||
| REF 13 | ClinicalTrials.gov (NCT00085826) A Phase III Study of the Efficacy of Taxotere/Aptosyn Versus Taxotere/Placebo in Non-Small Cell Lung Cancer Patients. U.S. National Institutes of Health. | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025495) | |||||
| REF 15 | Highly potent and selective chiral inhibitors of PDE5: an illustration of Pfeiffer's rule. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6033-6. | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018868) | |||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004678) | |||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018967) | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004019) | |||||
| REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005482) | |||||
| REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022583) | |||||
| REF 22 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6558). | |||||
| REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017097) | |||||
| REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014897) | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003084) | |||||
| REF 26 | Anti-platelet therapy: phosphodiesterase inhibitors.Br J Clin Pharmacol.2011 Oct;72(4):634-46. | |||||
| REF 27 | Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8. | |||||
| REF 28 | Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31. | |||||
| REF 29 | Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Int J Impot Res. 2002 Dec;14(6):466-71. | |||||
| REF 30 | Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. | |||||
| REF 31 | Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical d... Asian J Androl. 2009 Jul;11(4):435-42. | |||||
| REF 32 | Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 2000 Jul 1;60(13):3338-42. | |||||
| REF 33 | Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod. 2008 Sep;71(9):1513-7. | |||||
| REF 34 | Highlights of the society for medicinesresearch symposium held december 10th 2009 at the national heart and lung institute, London, UK. Drugs of the Future 2010, 35(4): 349-358. | |||||
| REF 35 | Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine. J Med Chem. 1994 Feb 18;37(4):476-85. | |||||
| REF 36 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 37 | Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme. Mol Pharmacol. 1999 Mar;55(3):508-14. | |||||
| REF 38 | Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs. 2008 Jun;17(6):855-64. | |||||
| REF 39 | Pfizer. Product Development Pipeline. March 31 2009. | |||||
| REF 40 | ClinicalTrials.gov (NCT00457457) Pfizer. Report of Pfizer. September 2 2008. | |||||
| REF 41 | Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3 (2H)-pyridazinones: novel positive inotropic agents for the treatment of conges... J Med Chem. 1984 Sep;27(9):1099-101. | |||||
| REF 42 | Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogues. J Med Chem. 1989 Jul;32(7):1450-7. | |||||
| REF 43 | 4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5. J Med Chem. 2000 Jun 29;43(13):2523-9. | |||||
| REF 44 | Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity. J Med Chem. 1994 Jun 24;37(13):2106-11. | |||||
| REF 45 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1304). | |||||
| REF 46 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 47 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 48 | A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5. Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6. | |||||
| REF 49 | DOI: 10.1021/op060099f | |||||
| REF 50 | The Gif system as a tool in medicinal chemistry: The oxidation of Sch 57726 under GoAggIII conditions, Bioorg. Med. Chem. Lett. 7(11):1381-1386 (1997). | |||||
| REF 51 | Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor. J Cardiovasc Pharmacol. 1996 Dec;28(6):862-9. | |||||
| REF 52 | Enzymological and pharmacological profile of T-0156, a potent and selective phosphodiesterase type 5 inhibitor. Eur J Pharmacol. 2002 Dec 5;456(1-3):91-8. | |||||
| REF 53 | Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. | |||||
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