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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32F3N3O4
Molecular Weight 495.5345
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SILODOSIN

SMILES

C[C@H](CC1=CC(C(N)=O)=C2N(CCCO)CCC2=C1)NCCOC3=CC=CC=C3OCC(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 495.5345
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

2008
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
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 Fri Dec 15 15:49:12 GMT 2023
Edited
by admin
on Fri Dec 15 15:49:12 GMT 2023
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
Silodosin [WHO-DD]
Common Name English
KMD-3213
Code English
SILODAL
Brand 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 Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
NDF-RT N0000175553
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
WHO-ATC G04CA04
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
LIVERTOX NBK548170
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
NCI_THESAURUS C29713
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
NDF-RT N0000000099
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
EMA ASSESSMENT REPORTS SILODYX (AUTHORIZED: PROSTATIC HYPERPLASIA)
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
WHO-VATC QG04CA04
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
Code System Code Type Description
SMS_ID
100000090781
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
EPA CompTox
DTXSID40167045
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
DRUG CENTRAL
4151
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
INN
8043
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
DRUG BANK
DB06207
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
CAS
160970-54-7
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
DAILYMED
CUZ39LUY82
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
RXCUI
720825
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY RxNorm
MERCK INDEX
m9912
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
SILODOSIN
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
NCI_THESAURUS
C81372
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
EVMPD
SUB23152
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
FDA UNII
CUZ39LUY82
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
ChEMBL
CHEMBL24778
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
IUPHAR
493
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
PUBCHEM
5312125
Created by admin on Fri Dec 15 15:49:12 GMT 2023 , Edited by admin on Fri Dec 15 15:49:12 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Selectivity of silodosin determined in cloned human α1-adrenergic receptor (α1-AR) subtypes in cultured Chinese hamster ovary cells.Silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by α1B blockade.
Ki
CUMULATIVE EXCRETION
URINE
BINDER->LIGAND
BINDING
OFF-TARGET->INHIBITOR
Selectivity of silodosin determined in cloned human α1-adrenergic receptor (α1-AR) subtypes in cultured Chinese hamster ovary cells.
Ki
CUMULATIVE EXCRETION
FECAL
OFF-TARGET->INHIBITOR
Related Record Type Details
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