U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32F3N3O4
Molecular Weight 495.5354
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SILODOSIN

SMILES

C[C@]([H])(Cc1cc2CCN(CCCO)c2c(c1)C(=N)O)NCCOc3ccccc3OCC(F)(F)F

InChI

InChIKey=PNCPYILNMDWPEY-QGZVFWFLSA-N
InChI=1S/C25H32F3N3O4/c1-17(30-8-12-34-21-5-2-3-6-22(21)35-16-25(26,27)28)13-18-14-19-7-10-31(9-4-11-32)23(19)20(15-18)24(29)33/h2-3,5-6,14-15,17,30,32H,4,7-13,16H2,1H3,(H2,29,33)/t17-/m1/s1

HIDE SMILES / InChI

Molecular Formula C25H32F3N3O4
Molecular Weight 495.5354
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Silodosin is a selective antagonsit of alpha-1a adrenergic receptor which was developed by Kissei Pharmaceutical. The drug was approved by FDA under the name Rapaflo for the treatment of signs and symptoms associated with benign prostatic hyperplasia.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.32 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
RAPAFLO

Approved Use

RAPAFLO, a selective alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).

Launch Date

1.22342395E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
61.6 ng/mL
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SILODOSIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
373.4 ng × h/mL
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SILODOSIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.3 h
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SILODOSIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SILODOSIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
48 mg 1 times / day multiple, oral
Highest studied dose
Dose: 48 mg, 1 times / day
Route: oral
Route: multiple
Dose: 48 mg, 1 times / day
Sources:
healthy, 19 - 45
n = 6
DLT: Postural hypotension...
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Other AEs: Nervous system disorder NOS, Fatigue...
Other AEs:
Nervous system disorder NOS (13%)
Fatigue (13%)
Dizziness (13%)
Hematuria (13%)
Leukocyturia (13%)
Sources: Page: p.1242
8 mg 1 times / day multiple, oral
Recommended
unhealthy
n = 466
Disc. AE: Retrograde ejaculation...
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Benign prostatic hyperplasia
Sex: M
Sources: Page: p.3
Other AEs: Intraoperative floppy iris syndrome...
AEs

AEs

AESignificanceDosePopulation
Postural hypotension DLT
48 mg 1 times / day multiple, oral
Highest studied dose
Dose: 48 mg, 1 times / day
Route: oral
Route: multiple
Dose: 48 mg, 1 times / day
Sources:
healthy, 19 - 45
n = 6
Dizziness 13%
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Fatigue 13%
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Hematuria 13%
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Leukocyturia 13%
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Nervous system disorder NOS 13%
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources: Page: p.1242
healthy, 23 ± 1.4
n = 8
Health Status: healthy
Age Group: 23 ± 1.4
Sex: M
Population Size: 8
Sources: Page: p.1242
Retrograde ejaculation 2.8%
Disc. AE
8 mg 1 times / day multiple, oral
Recommended
unhealthy
n = 466
Intraoperative floppy iris syndrome
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Benign prostatic hyperplasia
Sex: M
Sources: Page: p.3
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no (co-administration study)
Comment: silodosin did not significantly affect the PK of digoxin
Page: 5.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no (co-administration study)
Comment: furafylline did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: furafylline did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: coumarin did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: S-mephenytoin did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: sulfafenazole did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: quinidine did not affect silodosin metabolism
Page: 16.0
no
no (co-administration study)
Comment: diethyldithiocarbamate did not affect silodosin metabolism
Page: 16.0
yes
yes
yes (co-administration study)
Comment: ketaconzaole increased sildosin Cmax by 3.8-fold and AUC by 3.2-fold
Page: 5, 11, 12
yes
yes (co-administration study)
Comment: ketaconzaole increased sildosin Cmax by 3.8-fold and AUC by 3.2-fold
Page: 17.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues.
1995 Aug
Search for new alpha1a-adrenoceptor-selective antagonist for treating lower urinary tract symptoms associated with benign prostatic hyperplasia.
2007 Apr
Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia.
2007 Dec
Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia.
2007 Jul
Expressions and mechanical functions of alpha1-adrenoceptor subtypes in hamster ureter.
2007 Nov 14
Alpha1-adrenoceptors and ejaculatory function.
2007 Oct
Different affinities of native alpha1B-adrenoceptors for ketanserin between intact tissue segments and membrane preparations.
2008 Apr 28
[Multi-center trial on the early effects of silodosin on lower urinary tract symptoms associated with benign prostatic hyperplasia].
2008 Dec
In vivo study on the effects of alpha1-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in male dogs.
2008 Feb 2
Gateways to clinical trials.
2008 Jun
The involvement of urothelial alpha1A adrenergic receptor in controlling the micturition reflex.
2008 Oct
Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.
2008 Oct
Ejaculatory dysfunction caused by the new alpha1-blocker silodosin: A preliminary study to analyze human ejaculation using color Doppler ultrasonography.
2008 Oct
Computational studies of the binding site of alpha1A-adrenoceptor antagonists.
2008 Oct
Inhibition of Seminal emission is the main cause of anejaculation induced by a new highly selective alpha1A-blocker in normal volunteers.
2008 Sep
Effects of four different alpha(1)-adrenoceptor antagonists on alpha-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters.
2009 Aug
Mechanical function and gene expression of alpha(1)-adrenoceptor subtypes in dog intravesical ureter.
2009 Aug
Efficacy of silodosin for relieving benign prostatic obstruction: prospective pressure flow study.
2009 Dec
Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study.
2009 Dec
Gene expressions and mechanical functions of α1-adrenoceptor subtypes in mouse ureter.
2009 Dec
Efficacy of alpha-Adrenergic Receptor Blockers in the Treatment of Male Lower Urinary Tract Symptoms.
2009 Fall
Silodosin (Rapaflo) for benign prostatic hyperplasia.
2009 Jan 12
Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies.
2009 Jun
Short- and long-term effects of silodosin, a selective alpha 1A-adrenoceptor antagonist, on ejaculatory function in rats.
2009 Jun
Effects of silodosin and tamsulosin on the urethra and cardiovascular system in young and old dogs with benign prostatic hyperplasia.
2009 Jun 24
New drugs: milnacipran hydrochloride, fesoterodine fumarate, and silodosin.
2009 Mar-Apr
Silodosin: a selective alpha1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia.
2009 Nov
Determination of silodosin in human plasma by liquid chromatography-tandem mass spectrometry.
2009 Nov 1
Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration.
2009 Sep-Oct
The add-on effect of solifenacin for patients with remaining overactive bladder after treatment with tamsulosin for lower urinary tract symptoms suggestive of benign prostatic obstruction.
2010
Torsades de Pointes induced by a combination of garenoxacin and disopyramide and other cytochrome P450, family 3, subfamily A polypeptide-4-influencing drugs during hypokalemia due to licorice.
2010 Apr
Urodynamic effects of silodosin, a new alpha 1A-adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia.
2010 Apr
Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability.
2010 Dec
Ejaculation disorder is associated with increased efficacy of silodosin for benign prostatic hyperplasia.
2010 Dec
(RS)-1-[5-(2-Chloro-prop-yl)indolin-1-yl]ethanone.
2010 Dec 8
Silodosin for benign prostatic hyperplasia.
2010 Feb
Visualization and tissue distribution of alpha1L-adrenoceptor in human prostate by the fluorescently labeled ligand Alexa-488-silodosin.
2010 Feb
[Investigation of adverse events and the continuance rate of silodosin in all patients who received silodosin for lower urinary tract symptoms suggestive of benign prostatic hyperplasia].
2010 Jan
Effects of silodosin and naftopidil on the distal ureter and cardiovascular system in anesthetized dogs: comparison of potential medications for distal ureteral stone passage.
2010 Jan
Gateways to clinical trials.
2010 Jul-Aug
(RS)-1-(1-Acetyl-indolin-5-yl)-2-chloro-propan-1-one.
2010 Jun 9
Impact of dry ejaculation caused by highly selective alpha1A-blocker: randomized, double-blind, placebo-controlled crossover pilot study in healthy volunteer men.
2010 Mar
Lack of pharmacodynamic interaction of silodosin, a highly selective alpha1a-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafil and tadalafil in healthy men.
2010 Mar
Effects of the selective alpha 1a-adrenoceptor antagonist silodosin on ECGs of healthy men in a randomized, double-blind, placebo- and moxifloxacin-controlled study.
2010 May
Gateways to clinical trials.
2010 Nov
Editorial comment to short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia.
2010 Oct
Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia.
2010 Oct
Role of supraspinal and spinal alpha1-adrenergic receptor subtypes in micturition reflex in conscious rats.
2010 Oct
Selective α1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity.
2010 Oct
Silodosin in the treatment of benign prostatic hyperplasia.
2010 Oct 27
Patents

Sample Use Guides

The recommended dose is 8 mg orally once daily with a meal. The dose can be reduced to 4 mg for those with moderate renal impairment.
Route of Administration: Oral
In Vitro Use Guide
Sources: www.ncbi.nlm.nih.gov/pubmed/23226423
Human prostate tissue were treated with silodosin at 3 uM added 15 min before application of noradrenaline (30 uM) to study the inhibition of noradrenaline-activated Transcription Factors Elk1 and SRF.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:41:35 UTC 2021
Edited
by admin
on Sat Jun 26 05:41:35 UTC 2021
Record UNII
CUZ39LUY82
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SILODOSIN
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
RAPAFLO
Brand Name English
SILODOSIN [ORANGE BOOK]
Common Name English
KSO-0400
Common Name English
URIEF
Brand Name English
SILODOSIN [EMA EPAR]
Common Name English
(-)-1-(3-HYDROXYPROPYL)-5-((2R)-2-((2-(2-(2,2,2-TRIFLUOROETHOXY)PHENOXY)ETHYL)AMINO)PROPYL)-2,3-DIHYDRO-1H-INDOLE-7-CARBOXAMIDE
Systematic Name English
2,3-DIHYDRO-1-(3-HYDROXYPROPYL)-5-((2R)-2-((2-(2-(2,2,2-TRIFLUOROETHOXY)PHENOXY)ETHYL)AMINO)PROPYL)-1H-INDOLE-7-CARBOXAMIDE
Systematic Name English
KAD-3213
Code English
SILODOSIN [JAN]
Common Name English
SILODOSIN [INN]
Common Name English
SILODOSIN [MI]
Common Name English
SILODYX
Brand Name English
RAPILIF
Brand Name English
SILODOSIN [VANDF]
Common Name English
KMD-3213
Code English
SILODAL
Brand Name English
SILODOSIN [WHO-DD]
Common Name English
SILODOSIN [MART.]
Common Name English
UROREC
Brand Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS UROREC (AUTHORIZED: PROSTATIC HYPERPLASIA)
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
NDF-RT N0000175553
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
WHO-ATC G04CA04
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
LIVERTOX 886
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
NCI_THESAURUS C29713
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
NDF-RT N0000000099
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
EMA ASSESSMENT REPORTS SILODYX (AUTHORIZED: PROSTATIC HYPERPLASIA)
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
WHO-VATC QG04CA04
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
Code System Code Type Description
EPA CompTox
160970-54-7
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
DRUG CENTRAL
4151
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
INN
8043
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
DRUG BANK
DB06207
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
CAS
160970-54-7
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
RXCUI
720825
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M9912
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
SILODOSIN
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
NCI_THESAURUS
C81372
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
EVMPD
SUB23152
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
FDA UNII
CUZ39LUY82
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
ChEMBL
CHEMBL24778
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
IUPHAR
493
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
PUBCHEM
5312125
Created by admin on Sat Jun 26 05:41:36 UTC 2021 , Edited by admin on Sat Jun 26 05:41:36 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Selectivity of silodosin determined in cloned human ?1-adrenergic receptor (?1-AR) subtypes in cultured Chinese hamster ovary cells.Silodosin has greater affinity for the ?1A-adrenergic receptor than for the ?1B-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by ?1B blockade.
Ki
CUMULATIVE EXCRETION
URINE
BINDER->LIGAND
BINDING
OFF-TARGET->INHIBITOR
Selectivity of silodosin determined in cloned human ?1-adrenergic receptor (?1-AR) subtypes in cultured Chinese hamster ovary cells.
Ki
CUMULATIVE EXCRETION
FECAL
OFF-TARGET->INHIBITOR
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METABOLITE -> PARENT
MINOR
FECAL; PLASMA; URINE
METABOLITE -> PARENT
MEDIATOR-S9+NAD
MINOR
FECAL; PLASMA; URINE
METABOLITE LESS ACTIVE -> PARENT
Major in plasma
MAJOR
PLASMA; URINE
METABOLITE ACTIVE -> PRODRUG
Mediator: UDP-glucuronosyltransferase
MAJOR
PLASMA; URINE
METABOLITE LESS ACTIVE -> PARENT
Major in plasma and urine; S9+NAD mediator; Does not significanly contribute to the efficacy
MAJOR
FECAL; PLASMA; URINE
METABOLITE -> PARENT
MINOR
FECAL; PLASMA; URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC