General
Preferred name
SILDENAFIL
Synonyms
SILDENAFIL CITRATE ()
UK-92480 citrate ()
Sildenafil Mesylate ()
Rhucin ()
Sildenafil (citrate) ()
sildenafil, Kedem Pharmaceuticals ()
UK-92480 ()
UK-92480 (citrate) ()
UK-92480 Mesylate ()
Revatio, UK-92480, Viagra ()
Nipatra ()
Sildenafil ratiopharm ()
HIP-0908 ()
Aphrodil ()
Sildenafil teva ()
Revatio ()
Vizarsin ()
Sildenafil actavis ()
HIP0908 ()
Patrex ()
Viagra ()
UK-92480-10 ()
NSC-744009 ()
NSC-758669 ()
Sildenafil (as citrate) ()
UK-92,480-10 ()
Sildenafil-d3 ()
P&D ID
PD003443
CAS
171599-83-0
1308285-21-3
139755-83-2
1126745-90-1
Tags
natural product
drug
available
Approved by
EMA
FDA
First approval
1998
Drug Status
investigational
approved
withdrawn
Drug indication
Erectile dysfunction
Hereditary angioedema
Coronavirus Disease 2019 (COVID-19)
Impotence Therapy
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
INDICATION Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications: (1) the treatment of erectile dysfunction [A175582, L5611, F3853, F3856, F3886]; and (2) treatment of pulmonary hypertension, where: a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening [F3850]. The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy [F3850]. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) [F3850]; b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy [F3859]. In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy [F3859]; and c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity [F3883]. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease [F3883]. The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension [F3883]. Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease [F3883].
HALF-LIFE The terminal phase half-life observed for sildenafil is approximately 3 to 5 hours [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
MOA Sildenafil is an oral therapy for erectile dysfunction [A175582, F3853, F3856, F3886, L5611]. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis [A175582, F3853, F3856, F3886, L5611].; ; The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation [A175582, F3853, F3856, F3886, L5611]. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood [A175582, F3853, F3856, F3886, L5611].; ; Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP [A175582, F3853, F3856, F3886, L5611]. Sildenafil has a peripheral site of action on erections [A175582, F3853, F3856, F3886, L5611]. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue [A175582, F3853, F3856, F3886, L5611]. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP [A175582, F3853, F3856, F3886, L5611]. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects [A175582, F3853, F3856, F3886, L5611].; ; Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature [A175579, F3850, F3859, F3883, L5614]. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation [A175579, F3850, F3859, F3883, L5614]. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation [A175579, F3850, F3859, F3883, L5614].
INDICATION Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications:; ; (1) the treatment of erectile dysfunction [A175582, L5611, F3853, F3856, F3886]; and; ; (2) treatment of pulmonary hypertension, where:; a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening [F3850]. The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy [F3850]. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) [F3850];; ; b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy [F3859]. In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy [F3859]; and; ; c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity [F3883]. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease [F3883]. The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension [F3883]. Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease [F3883].
DESCRIPTION Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor.
Marketed formulations may contain ildenafil citrate (PubChem CID 62853). (GtoPdb)
MOA Sildenafil is an oral therapy for erectile dysfunction [A175582, F3853, F3856, F3886, L5611]. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis [A175582, F3853, F3856, F3886, L5611]. The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation [A175582, F3853, F3856, F3886, L5611]. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood [A175582, F3853, F3856, F3886, L5611]. Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP [A175582, F3853, F3856, F3886, L5611]. Sildenafil has a peripheral site of action on erections [A175582, F3853, F3856, F3886, L5611]. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue [A175582, F3853, F3856, F3886, L5611]. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP [A175582, F3853, F3856, F3886, L5611]. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects [A175582, F3853, F3856, F3886, L5611]. Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature [A175579, F3850, F3859, F3883, L5614]. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation [A175579, F3850, F3859, F3883, L5614]. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation [A175579, F3850, F3859, F3883, L5614].
METABOLISM The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic isoenzymes [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The predominant circulating metabolite results from the N-demethylation of sildenafil [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This particular resultant metabolite possesses a phosphodiesterase selectivity that is similar to the parent sildenafil molecule and a corresponding in vitro potency for PDE5 that is approximately 50% that of the parent drug [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
ABSORPTION Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes) of oral administration in a fasting patient [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Moreover, the mean absolute bioavailability observed for sildenafil is about 41% (from a range of 25-63%) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. In particular, after oral three times a day dosing of sildenafil, the AUC and Cmax increase in proportion with dose over the recommended dosage range of 25-100 mg [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
METABOLISM The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic isoenzymes [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The predominant circulating metabolite results from the N-demethylation of sildenafil [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This particular resultant metabolite possesses a phosphodiesterase selectivity that is similar to the parent sildenafil molecule and a corresponding in vitro potency for PDE5 that is approximately 50% that of the parent drug [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].; ; In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects [A175654, F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
ABSORPTION Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes) of oral administration in a fasting patient [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Moreover, the mean absolute bioavailability observed for sildenafil is about 41% (from a range of 25-63%) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. In particular, after oral three times a day dosing of sildenafil, the AUC and Cmax increase in proportion with dose over the recommended dosage range of 25-100 mg [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].; ; When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].; ; Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614].
DESCRIPTION inhibitor of phosphodiesterase 5A (Informer Set)
DESCRIPTION Orally active, potent PDE5 inhibitor (Tocriscreen Plus)
DESCRIPTION Sildenafil is an inhibitor of phosphodiesterase 5. (BOC Sciences Bioactive Compounds)
Cell lines
0
Organisms
2
Compound Sets
39
AdooQ Bioactive Compound Library
A12631
A10841
A16142
Axon Medchem Screening Library
2046
BOC Sciences Bioactive Compounds
sildenafil-mesylate-cas-1308285-21-3-291197
Cayman Chemical Bioactives
10008671
14008
18261
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL192
CHEMBL1737
ChEMBL Drugs
CHEMBL192
CHEMBL1737
Concise Guide to Pharmacology 2017/18
4743
Concise Guide to Pharmacology 2019/20
4743
Concise Guide to Pharmacology 2021/22
4743
Concise Guide to Pharmacology 2023/24
4743
Drug Repurposing Hub
DrugBank
DB00203
DrugBank Approved Drugs
DB00203
DrugCentral
2441
DrugCentral Approved Drugs
2441
DrugMAP
DM3ADGP
DM4YDAJ
DrugMAP Approved Drugs
DM3ADGP
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101137
Guide to Pharmacology
4743
Informer Set
27872
Ki Database
sildenafil
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL192
CHEMBL1737
Mcule NIBR MoA Box Subset
MCULE-2481702478
MedChem Express Bioactive Compound Library
HY-15025
HY-15025A
NCATS Inxight Approved Drugs
3M7OB98Y7H
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
sildenafil
Sildenafil-citrate
sildenafil-mesylate
TargetMol Bioactive Compound Library
T0467
The Spectrum Collection
Tocriscreen Plus
3784
VGSC-DB
NA0062
NA0063
Withdrawn 2.0
EMA39
ZINC Tool Compounds
ZINC000019796168
External IDs
104
Properties
(calculated by RDKit )
Molecular Weight
474.2
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
1
Rotatable Bonds
7
Ring Count
4
Aromatic Ring Count
3
cLogP
1.61
TPSA
113.42
Fraction CSP3
0.5
Chiral centers
0.0
Largest ring
6.0
QED
0.55
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
PDE5A
Phosphodiesterase 5A
PDE5
PDE6
PDE5A, PDE6G, PDE6H, SLCO1B1, SLCO1B3
PDE5 inhibitor
Bacterial
Phosphodiesterase (PDE)
PDE
Compound status
FDA
Target Type
Enzymes
MOA
phosphodiesterase inhibitor
phosphodiesterase PDE5A Inhibitors
Pathway
Metabolism
Anti-infection
Apoptosis
Autophagy
Metabolic Enzyme/Protease
Member status
member
Indication
erectile dysfunction
ATC
G04BE03
Therapeutic Class
Antiviral Agents
VGSC Target
Nav1.5
Source data