| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 2g |
|
||
| 5g |
|
||
| Other Sizes |
|
Purity: ≥98%
Silodosin (KMD-3213; KMD3213; KAD3213; KAD-3213; Silodosin; trade names Rapaflo, Silodal, Silodyx, Rapilif, Urief, Urorec) is a highly selective alpha1A/α1A-adrenoceptor antagonist that was approved for the treatment of BPH-benign prostatic hyperplasia.
| Targets |
α1A-AR ( Ki = 0.036 nM ); α1B-AR ( Ki = 21 nM ); α1D-AR ( Ki = 2 nM )
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Cell Assay |
Cell Line: TCCSUP; UMUC3 and 647V cells
Concentration: 0.1, 0.5, 3.0, or 10 µM Incubation Time: 24 hours Result: Decreases ELK1 in bladder cancer cells |
|
| Animal Protocol |
Sprague Dawley rats
0.1-0.3mg/kg Intravenous injection |
|
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The absolute bioavailability is approximately 32%. Following oral administration of silodosin 8 mg once daily in healthy male subjects, Cmax was 61.6 ± 27.54 ng/mL and AUC was 373.4 ± 164.94 ng x hr/mL. The Tmax was 2.6 ± 0.90 hours. Silodosin glucuronide or KMD-3213G, the main metabolite of silodosin, has an AUC three- or four fold higher than for the parent compound. A moderate fat or calorie meal reduces Cmax by 18% to 43% and AUC by 4% to 49%, as well as Tmax by about one hour. However, the US prescribing information recommends drug intake with meals to avoid the potential adverse effects associated with high plasma drug concentrations. At 10 days following oral administration of radiolabelled silodosin, about 33.5% of the dose was recovered in urine and 54.9% was recovered in feces. Silodosin has an apparent volume of distribution of 49.5 L. After intravenous administration, the plasma clearance of silodosin was approximately 10 L/hour. Metabolism / Metabolites The main metabolite of silodosin is silodosin glucuronide (KMD-3213G), which is a pharmacologically active metabolite formed by direct glucuronide conjugation mediated by UDP-glucuronosyltransferase 2B7 (UGT2B7). Silodosin glucuronide reaches plasma exposure (AUC) approximately four times greater than that of silodosin. The second major metabolite, KMD-3293, is formed from dehydrogenation catalyzed by alcohol and aldehyde dehydrogenases. KMD-3293 has negligible pharmacological activity and reaches plasma exposures similar to that of silodosin. Silodosin is also metabolized by CYP3A4, which catalyzes the oxidation reaction. Other than glucuronidation, dehydrogenation, and oxidation as its main metabolic pathways, silodosin can also undergo dealkylation (KMD-3289), N-dealkylation, hydroxylation, glucosylation, and sulfate conjugation. Metabolites of silodosin can undergo a series of further metabolic pathways. Biological Half-Life The elimination half-life of silodosin is 13.3 ± 8.07 hours. KMD-3213G, the main metabolite of silodosin, has an extended half-life of approximately 24 hours. |
|
| Toxicity/Toxicokinetics |
Hepatotoxicity
Silodosin has been associated with a low rate of serum aminotransferase elevations ( Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury). Protein Binding Silodosin is approximately 97% protein bound. |
|
| References |
|
|
| Additional Infomation |
Pharmacodynamics
Silodosin is an antagonist of α1-adrenoceptors. It has the highest selectivity for the α1A-adrenoceptor subtype, with a 162-fold greater affinity than α1B-adrenoceptor and about a 50-fold greater affinity than for α1D-adrenoceptor. In clinical trials, silodosin improved maximum urinary flow rate, voiding symptoms, and storage symptoms of benign prostatic hyperplasia. Following oral administration, silodosin had a rapid onset of effect in men, with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose. Silodosin inhibited the human ether-a-go-go-related gene (HERG) tail current; however, it has weak cardiovascular effects. As with all α1-adrenoceptor antagonists blocking α1-adrenoceptors in the iris dilator muscle, silodosin may cause intraoperative floppy iris syndrome (IFIS), which is characterized by small pupils and iris billowing during cataract surgery in patients taking α1-AR antagonists. |
| Molecular Formula |
C25H32F3N3O4
|
|---|---|
| Molecular Weight |
495.53
|
| Exact Mass |
495.234
|
| Elemental Analysis |
C, 60.60; H, 6.51; F, 11.50; N, 8.48; O, 12.91
|
| CAS # |
160970-54-7
|
| Related CAS # |
Silodosin-d4; 1426173-86-5
|
| PubChem CID |
5312125
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
601.4±55.0 °C at 760 mmHg
|
| Melting Point |
107 °C
|
| Flash Point |
317.5±31.5 °C
|
| Vapour Pressure |
0.0±1.8 mmHg at 25°C
|
| Index of Refraction |
1.552
|
| LogP |
2.52
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
35
|
| Complexity |
654
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
FC(C([H])([H])OC1=C([H])C([H])=C([H])C([H])=C1OC([H])([H])C([H])([H])N([H])[C@]([H])(C([H])([H])[H])C([H])([H])C1C([H])=C(C(N([H])[H])=O)C2=C(C=1[H])C([H])([H])C([H])([H])N2C([H])([H])C([H])([H])C([H])([H])O[H])(F)F
|
| InChi Key |
PNCPYILNMDWPEY-QGZVFWFLSA-N
|
| InChi Code |
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
|
| Chemical Name |
1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-2,3-dihydroindole-7-carboxamide
|
| Synonyms |
KAD 3213; KMD 3213; KMD 3213; KAD 3213; KMD-3213; KMD3213; KAD 3213; KAD3213; Silodosin; trade names: Rapaflo; Silodyx, Rapilif; Silodal; Urief; Urorec
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0180 mL | 10.0902 mL | 20.1804 mL | |
| 5 mM | 0.4036 mL | 2.0180 mL | 4.0361 mL | |
| 10 mM | 0.2018 mL | 1.0090 mL | 2.0180 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Comparison of the long-term efficacy of silodosin and tamsulodin for the tratment of benign prostatic hyperplasia
CTID: UMIN000008538
Phase: Phase IV Status: Complete: follow-up complete
Date: 2012-08-01
|
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
