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Drug-Target Interaction

Drug

show drug details
PubChem ID:5212
Structure:
Synonyms:
1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-y
1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine
1-((3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine citrate
139755-83-2
171599-83-0
1udt
1xos
2h42
5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[5,4-e]pyrimidin-7-one
5-{2-(ethyloxy)-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
Ambap1012
BAS 04213629
BSPBio_003424
C07259
C22H30N6O4S
CHEBI:9139
DB00203
DivK1c_006894
HSDB 7305
KBio1_001838
KBio2_002035
KBio2_004603
KBio2_007171
KBio3_002927
KBioGR_001052
KBioSS_002035
KS-1112
LS-111655
MLS001240224
MLS001304737
NCGC00095099-01
NCGC00095099-02
NCGC00159496-02
Piperazine, 1-((3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methyl-
Sildenafil
SILDENAFIL CITRATE
Sildenafil [INN:BAN]
SMR000752512
SPBio_001775
SpecPlus_000798
SPECTRUM1504099
Spectrum2_001648
Spectrum3_001892
Spectrum4_000586
Spectrum5_001508
Spectrum_001555
UK 92480-10
UK-92,480-10
VIA
VIAGRA
ATC-Codes:
Side-Effects:
Side-EffectFrequency
headache0.11199999
flushing0.064
dyspepsia0.05
nasal congestion0.031999998
blurred vision0.03
urinary tract infection0.025999999
diarrhea0.022
dizziness0.015999999
rash0.015999999
abnormal vision0.011363637
coronary artery disease0.0010
swelling0.0010
hematuria0.0010
diabetes0.0010
vascular disease0.0010
hemorrhage0.0010
diplopia0.0010
hypertension0.0010
vitreous detachment0.0010
vomiting0.0010
hyperlipidemia0.0010
epistaxis0.0010
edema0.0010
neuropathy0.0010
loss of vision0.0010
arrhythmia0.0010
myocardial infarction0.0010
intracerebral hemorrhages0.0010
anxiety0.0010
priapism0.0010
transient ischemic attack0.0010
seizure0.0010
hearing loss0.0010
erythema0
upper respiratory tract infection0
sexual dysfunction0
paresthesia0
urticaria0
urinary incontinence0
pharyngitis0
syncope0
renal failure0
tremor0
skin ulcer0
shock0
stomatitis0
sweating0
synovitis0
tachycardia0
tenosynovitis0
pruritus0
shoulder pain0
rhinitis0
tinnitus0
retinal hemorrhage0
tooth disorder0
sinusitis0
varicose vein0
vertigo0
myalgia0
hypoxia0
global amnesia0
rectal hemorrhage0
dry eyes0
transient global amnesia0
photosensitivity0
ecg abnormal0
urinary frequency0
lung cancer0
skin carcinoma0
acne0
hyperuricemia0
cardiomyopathy0
insomnia0
malaise0
vascular anomaly0
weight gain0
dry mouth0
cerebral thrombosis0
chills0
agitation0
photophobia0
peripheral edema0
cataract0
lower respiratory infection0
mouth ulceration0
migraine0
myocardial ischemia0
liver function tests abnormal0
bone pain0
eye pain0
allergic reaction0
abdominal pain0
cough0
cystitis0
deafness0
dysphagia0
dermatitis0
exfoliative dermatitis0
contact dermatitis0
somnolence0
dyspnea0
ear pain0
abdominal distention0
endocrine disorders0
eructation0
esophagitis0
fever0
constipation0
conjunctivitis0
colitis0
anemia0
angina pectoris0
anorexia0
arthralgia0
arthritis0
asthenia0
asthma0
ataxia0
av block0
back pain0
balanitis0
bronchitis0
cellulitis0
cerebrovascular disorder0
chest pain0
flatulence0
furunculosis0
gastritis0
postural hypotension0
infection0
influenza0
arthrosis0
lacrimation disorder0
laryngitis0
leukopenia0
mediastinal disorders0
nail disorder0
nausea0
nervousness0
neuralgia0
nocturia0
pain0
pain in limb0
hypotension0
hypokalemia0
breast enlargement0
gastroenteritis0
gastroesophageal reflux0
gingivitis0
glossitis0
gout0
cardiac arrest0
heart disease0
heart failure0
hemoptysis0
hernia0
herpes simplex0
hyperesthesia0
hyperglycemia0
hypernatremia0
hyperthyroidism0
palpitations0

Target

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Uniprot ID:PDE5A_HUMAN
Synonyms:
CGB-PDE
cGMP-binding cGMP-specific phosphodiesterase
cGMP-specific 3',5'-cyclic phosphodiesterase
EC-Numbers:3.1.4.35
Organism:Homo sapiens
Human
PDB IDs:1RKP 1T9R 1T9S 1TBF 1UDT 1UDU 1UHO 1XOZ 1XP0 2CHM 2H40 2H42 2H44 3B2R 3BJC 3HC8 3HDZ
Structure:
3HDZ

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----
----
----
--1-
--1.6-
--1.78-
--3-
--3.5-
--3.5-
--3.6-
--3.9-
--6.6-
1.87---
--11-
1.91---
--20-
--53-
10---
--75-
---8.7
---42

References:

12695418
PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers.. Masashi Kimura; Yukihito Higashi; Keiko Hara; Kensuke Noma; Satoshi Sasaki; Keigo Nakagawa; Chikara Goto; Tetsuya Oshima; Masao Yoshizumi; Kazuaki Chayama (2003) Hypertension display abstract
Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3+/-2.0 to 12.5+/-3.5 mL/min per 100 mL tissue in smokers and from 12.6+/-5.6 to 19.6+/-8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3+/-3.9 to 15.1+/-4.3 mL/min per 100 mL tissue in smokers and from 14.8+/-5.2 to 18.4+/-6.0 mL/min/100 mL tissue in nonsmokers (P
15476742
Absence of clinically important HERG channel blockade by three compounds that inhibit phosphodiesterase 5--sildenafil, tadalafil, and vardenafil.. R Dustan Sarazan; William J CrumbJr; Charles M BeasleyJr; Jeffrey T Emmick; Kenneth M Ferguson; Christine A Strnat; Peter J Sausen (2004) European journal of pharmacology display abstract
Compounds that inhibit phosphodiesterase 5 (PDE5) have been developed for the treatment of erectile dysfunction. Because men with erectile dysfunction frequently have comorbid cardiovascular disease, they may have limited cardiac repolarization reserve and be at risk of arrhythmia if treated with medications that prolong ventricular repolarization. The human ether-a-go-go related gene (HERG) channel is important for repolarization in human myocardium and is a common target for drugs that prolong the QT interval. We studied the ability of three compounds that inhibit PDE5--sildenafil, tadalafil, and vardenafil--to block the HERG channel. Using a whole cell variant of the patch-clamp method, the HERG current was measured in a stably transfected human embryonic kidney cell line expressing the HERG channel. The compounds produced dose-dependent reductions in HERG current amplitude over a concentration range of 0.1 to 100 microM. The IC50 values were 12.8 microM for vardenafil and 33.3 microM for sildenafil. Because the maximum soluble concentration of tadalafil (100 microM) produced only a 50.9% inhibition of the HERG current amplitude, the IC50 value for tadalafil could not be determined with the Hill equation. Tadalafil had the weakest capacity to block the HERG channel, producing a 50.9% blockade at the maximum soluble concentration (100 microM), compared with 86.2% for vardenafil (100 microM) and 75.2% for sildenafil (100 microM). In conclusion, the concentrations of the PDE5 inhibitors required to evoke a 50% inhibition of the HERG current were well above reported therapeutic plasma concentrations of free and total compound. None of the three compounds was a potent blocker of the HERG channel.
15878705
cGMP-phosphodiesterase antagonists inhibit Ca2+-influx in Dictyostelium discoideum and bovine cyclic-nucleotide-gated-channel.. Daniel F Lusche; Hiroshi Kaneko; Dieter Malchow (2005) European journal of pharmacology display abstract
We used antagonists of cGMP-phosphodiesterases to examine the role of cGMP for light-scattering oscillations and cAMP-induced Ca(2+)-influx in Dictyostelium discoideum, however, SCH 51866 (cis-5,6a,7,8,9,9a-hexahydro-2-[4-(trifluoromethyl)phenylmethyl]-5-methyl-cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-one) and sildenafil citrate (1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1-H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate) were poor inhibitors of cGMP-hydrolysis. Instead, SCH 51866 (IC(50) = 16 microM) and sildenafil, blocked chemoattractant (cAMP)-induced Ca(2+)-influx as determined with a Ca(2+)-specific electrode. SCH 51866 (150 microM) affected neither spontaneous cGMP transients during light-scattering-oscillations nor cAMP-mediated K(+)-efflux. SCH 51866 and sildenafil are competitive inhibitors of cGMP phosphodiesterases. However, the activity of cGMP-dependent protein kinase Ialpha (PKGIalpha) was not altered by SCH 51866 (150 microM). By contrast, patch-clamp measurements of bovine cone cGMP-gated-channels (cyclic-nucleotide-gated-channel, CNGA3), stably expressed in human embryonic kidney cells, HEK 293 cells, revealed reversible, competitive and dose-dependent inhibition of sodium currents by SCH 51866 (IC(50) = 25 microM) and sildenafil, but not by another inhibitor of cGMP-phosphodiesterases, UK 114,542. The possibility that D. discoideum cells also express a cGMP-regulated channel is supported by our finding that LY 83583 (6-(phenylamino)-5,8-quinolinedione) (35 microM), known to inhibit cyclic-nucleotide-gated-channels as well as guanylyl-cyclases, reduced cAMP-induced Ca(2+)-influx in D. discoideum, but did not affect cAMP-induced cGMP accumulation. Utilizing a PDED null strain that exhibits a prolonged and elevated cGMP transient following receptor activation, we found that the inhibition of Ca(2+)-influx by SCH 51866 in the wildtype was absent in the mutant. Our results show that SCH 51866 and sildenafil are antagonists of a Ca(2+)-permeable channel (CNGA3) and that both compete with cGMP for a regulatory site of Ca(2+)-influx in D. discoideum.
16182282
Phosphodiesterase 5 and effects of sildenafil on cerebral arteries of man and guinea pig.. Christina Kruuse; Tejvir S Khurana; Sergei D Rybalkin; Steffen Birk; Ulla Engel; Lars Edvinsson; Jes Olesen (2005) European journal of pharmacology display abstract
Sildenafil (Viagra), a selective inhibitor of phosphodiesterase 5 (PDE5), induces headache and migraine. Although previously supposed to be a "vascular" headache, no significant cerebral artery dilatation was found in vivo. Thus, we hypothesised that PDE5 may not be present or that sildenafil is less effective on the cGMP hydrolysis in cerebral arteries, and that sildenafil may not be an effective dilator of cerebral arteries under baseline conditions. We evaluated the presence of PDE5 mRNA and protein in human arteries. Furthermore, the effects of two selective PDE5 inhibitors, sildenafil and UK-114,542, and a PDE1 inhibitor UK-90,234 on cGMP hydrolysis were investigated in human and guinea pig cerebral arteries. The vasoactive responses of the compounds were evaluated in guinea pig basilar arteries in vitro, with concomitant measurements of cAMP and cGMP. PDE5 was found in human middle cerebral arteries. Sildenafil and UK-114,542 inhibited cGMP hydrolysis concentration-dependently in both species. In guinea pig arteries, sildenafil induced an endothelium-dependent vasodilatation only at concentrations above 10 nM, which was augmented by sodium nitroprusside and attenuated by reduction of cGMP, but was cGMP independent at high concentrations. UK-114,542 was more and UK-90,234 was less potent than sildenafil. In conclusion, PDE5 is present in human and guinea pig cerebral arteries, and is inhibited by sildenafil at micromolar levels. Sildenafil in vitro is a poor dilator of guinea pig cerebral arteries unless a nitric oxide donor is co-administered, corresponding to the previous findings in vivo.
16813753
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