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
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
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 |
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL229 |
0.32 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | RAPAFLO Approved UseRAPAFLO, a selective alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Launch Date2008 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 6 Sources: |
DLT: Postural hypotension... Dose limiting toxicities: Postural hypotension Sources: |
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%) Sources: Page: p.1242Fatigue (13%) Dizziness (13%) Hematuria (13%) Leukocyturia (13%) |
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.6 |
unhealthy n = 466 Health Status: unhealthy Condition: Benign prostatic hyperplasia Sex: M Population Size: 466 Sources: Page: p.6 |
Disc. AE: Retrograde ejaculation... AEs leading to discontinuation/dose reduction: Retrograde ejaculation (2.8%) Sources: Page: p.6 |
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... Other AEs: Intraoperative floppy iris syndrome Sources: Page: p.3 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: healthy Age Group: 19 - 45 Sex: M Population Size: 6 Sources: |
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 Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.6 |
unhealthy n = 466 Health Status: unhealthy Condition: Benign prostatic hyperplasia Sex: M Population Size: 466 Sources: Page: p.6 |
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 |
Overview
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5, 12 |
no | |||
Page: 5.0 |
no | no (co-administration study) Comment: silodosin did not significantly affect the PK of digoxin Page: 5.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 61.0 |
no | |||
Page: 16.0 |
no | no (co-administration study) Comment: furafylline did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: furafylline did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: coumarin did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: S-mephenytoin did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: sulfafenazole did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: quinidine did not affect silodosin metabolism Page: 16.0 |
||
Page: 16.0 |
no | no (co-administration study) Comment: diethyldithiocarbamate did not affect silodosin metabolism Page: 16.0 |
||
Page: 11.0 |
yes | |||
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: 5, 11, 12 |
||
Page: 17.0 |
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 2, 31 |
PubMed
Title | Date | PubMed |
---|---|---|
KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. | 1995 Aug |
|
Effects of KMD-3213, a uroselective alpha 1A-adrenoceptor antagonist, on the tilt-induced blood pressure response in normotensive rats. | 2002 Oct |
|
KMD 3213: KAD 3213, silodosin. | 2004 |
|
Cardiovascular effects of the selective alphalA-adrenoceptor antagonist silodosin (KMD-3213), a drug for the treatment of voiding dysfunction. | 2006 |
|
[Alpha1-adrenoceptor subtypes and alpha1-adrenoceptor antagonists]. | 2006 Mar |
|
Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. | 2006 Nov |
|
[Pharmacological and clinical profile of silodosin (URIEF Cap. 2 mg, 4 mg)]. | 2006 Oct |
|
Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. | 2007 Dec |
|
Identification of alpha-1L and alpha-1A adrenoceptors in human prostate by tissue segment binding. | 2007 Jan |
|
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 |
|
[Multi-center trial on the early effects of silodosin on lower urinary tract symptoms associated with benign prostatic hyperplasia]. | 2008 Dec |
|
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 |
|
Effects of four different alpha(1)-adrenoceptor antagonists on alpha-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters. | 2009 Aug |
|
Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study. | 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 |
|
Short- and long-term effects of silodosin, a selective alpha 1A-adrenoceptor antagonist, on ejaculatory function in rats. | 2009 Jun |
|
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 |
|
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 |
|
Gateways to clinical trials. | 2010 Jul-Aug |
|
(RS)-1-(1-Acetyl-indolin-5-yl)-2-chloro-propan-1-one. | 2010 Jun 9 |
|
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 |
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:49:12 GMT 2023
by
admin
on
Fri Dec 15 15:49:12 GMT 2023
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Record UNII |
CUZ39LUY82
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
UROREC (AUTHORIZED: PROSTATIC HYPERPLASIA)
Created by
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NDF-RT |
N0000175553
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WHO-ATC |
G04CA04
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LIVERTOX |
NBK548170
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NCI_THESAURUS |
C29713
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NDF-RT |
N0000000099
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EMA ASSESSMENT REPORTS |
SILODYX (AUTHORIZED: PROSTATIC HYPERPLASIA)
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WHO-VATC |
QG04CA04
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DTXSID40167045
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4151
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DB06207
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CUZ39LUY82
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720825
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m9912
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SILODOSIN
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C81372
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SUB23152
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CUZ39LUY82
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CHEMBL24778
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493
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5312125
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Related Record | Type | Details | ||
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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
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CUMULATIVE EXCRETION |
URINE
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BINDER->LIGAND |
BINDING
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OFF-TARGET->INHIBITOR |
Selectivity of silodosin determined in cloned human α1-adrenergic receptor (α1-AR) subtypes in cultured Chinese hamster ovary cells.
Ki
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CUMULATIVE EXCRETION |
FECAL
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OFF-TARGET->INHIBITOR |
Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE -> PARENT |
MINOR
FECAL; PLASMA; URINE
|
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METABOLITE -> PARENT |
MEDIATOR-S9+NAD
MINOR
FECAL; PLASMA; URINE
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METABOLITE LESS ACTIVE -> PARENT |
Major in plasma
MAJOR
PLASMA; URINE
|
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METABOLITE ACTIVE -> PRODRUG |
Mediator: UDP-glucuronosyltransferase
MAJOR
PLASMA; URINE
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METABOLITE LESS ACTIVE -> PARENT |
Major in plasma and urine; S9+NAD mediator; Does not significanly contribute to the efficacy
MAJOR
FECAL; PLASMA; URINE
|
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|
METABOLITE -> PARENT |
MINOR
FECAL; PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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