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=CC2=C(N(CCCO)CC2)C(=C1)C(N)=O)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 Health Status: healthy Age Group: 19 - 45 Sex: M Sources: |
DLT: Postural hypotension... Dose limiting toxicities: Postural hypotension Sources: |
12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
Other AEs: Nervous system disorder NOS, Fatigue... Other AEs: Nervous system disorder NOS (13%) Sources: Fatigue (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: |
unhealthy |
Disc. AE: Retrograde ejaculation... AEs leading to discontinuation/dose reduction: Retrograde ejaculation (2.8%) Sources: |
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: |
unhealthy Health Status: unhealthy Sex: M Sources: |
Other AEs: Intraoperative floppy iris syndrome... Other AEs: Intraoperative floppy iris syndrome Sources: |
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 Health Status: healthy Age Group: 19 - 45 Sex: M Sources: |
Dizziness | 13% | 12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
Fatigue | 13% | 12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
Hematuria | 13% | 12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
Leukocyturia | 13% | 12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
Nervous system disorder NOS | 13% | 12 mg single, oral Highest studied dose |
healthy, 23 ± 1.4 |
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: |
unhealthy |
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: |
unhealthy Health Status: unhealthy Sex: M Sources: |
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 |
|
Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. | 2004 Sep 1 |
|
Cardiovascular effects of the selective alphalA-adrenoceptor antagonist silodosin (KMD-3213), a drug for the treatment of voiding dysfunction. | 2006 |
|
Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the obstructive component of benign prostatic hyperplasia. | 2006 |
|
[Pharmacokinetic profile of silodosin in clinical practice]. | 2006 Mar |
|
[Toxicity profile of silodosin (KMD-3213)]. | 2006 Mar |
|
[Pharmacokinetics and disposition of silodosin (KMD-3213)]. | 2006 Mar |
|
[Duration of action of silodosin (KMD-3213) against phenylephrine-induced increase in intraurethral pressure in rats]. | 2006 Mar |
|
[Effect of silodosin on intraurethral pressure increase induced by hypogastric nerve stimulation in dogs with benign prostatic hyperplasia]. | 2006 Mar |
|
[Effects of silodosin (KMD-3213) on phenylephrine-induced increase in intraurethral pressure and blood pressure in rats--study of the selectivity for lower urinary tract]. | 2006 Mar |
|
[Alpha1-adrenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213)]. | 2006 Mar |
|
[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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Urodynamic effects of silodosin, a new alpha 1A-adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia. | 2010 Apr |
|
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 |
|
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 |
|
(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 |
|
Gateways to clinical trials. | 2010 Nov |
|
Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia. | 2010 Oct |
|
Selective α1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity. | 2010 Oct |
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:09:49 GMT 2025
by
admin
on
Mon Mar 31 18:09:49 GMT 2025
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Record UNII |
CUZ39LUY82
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Record Status |
Validated (UNII)
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Record Version |
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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
Created by
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WHO-ATC |
G04CA04
Created by
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LIVERTOX |
NBK548170
Created by
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NCI_THESAURUS |
C29713
Created by
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NDF-RT |
N0000000099
Created by
admin on Mon Mar 31 18:09:49 GMT 2025 , Edited by admin on Mon Mar 31 18:09:49 GMT 2025
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EMA ASSESSMENT REPORTS |
SILODYX (AUTHORIZED: PROSTATIC HYPERPLASIA)
Created by
admin on Mon Mar 31 18:09:49 GMT 2025 , Edited by admin on Mon Mar 31 18:09:49 GMT 2025
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WHO-VATC |
QG04CA04
Created by
admin on Mon Mar 31 18:09:49 GMT 2025 , Edited by admin on Mon Mar 31 18:09:49 GMT 2025
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100000090781
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DTXSID40167045
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4151
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8043
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DB06207
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160970-54-7
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CUZ39LUY82
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720825
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m9912
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PRIMARY | Merck Index | ||
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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 ?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
|
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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 ?1-adrenergic receptor (?1-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 | ||
---|---|---|---|---|
|
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 | ||
---|---|---|---|---|
|
IMPURITY -> PARENT |
|
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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