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Identification
- Summary
Silodosin is an alpha-1 adrenergic receptor antagonist used to treat symptoms associated with benign prostatic hyperplasia (BPH).
- Brand Names
- Rapaflo, Silodyx, Urorec
- Generic Name
- Silodosin
- DrugBank Accession Number
- DB06207
- Background
Silodosin is a selective antagonist of alpha(α)-1 adrenergic receptors that binds to the α1A subtype with the highest affinity. α1-adrenergic receptors regulate smooth muscle tone in the bladder neck, prostate, and prostatic urethra: the α1A subtype accounts for approximately 75% of α1-adrenoceptors in the prostate.2
Silodosin was first approved by the FDA in October 2008 2 and it is also approved in Europe and Canada. Silodosin is available as oral capsules with common trade names Rapaflo and Urorec. It is indicated for the symptomatic treatment of benign prostatic hyperplasia in adults.7 Most commonly affecting males over the age of 40 years, benign prostatic hyperplasia is the non-malignant enlargement of the prostate gland, associated with lower urinary tract symptoms that have a negative impact on the quality of life of patients.2 Silodosin works by binding to α1A-adrenoceptors with high affinity and relaxing the lower urinary tract, thereby improving urinary symptoms and alleviating bladder outlet obstruction.6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Silodosin (DB06207)
- Weight
- Average: 495.5345
Monoisotopic: 495.234491142 - Chemical Formula
- C25H32F3N3O4
- Synonyms
- Silodosin
- Silodosina
- External IDs
- KAD 3213
- KAD-3213
- KMD 3213
- KMD-3213
Pharmacology
- Indication
Silodosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). It is not indicated for the treatment of hypertension.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Benign prostatic hyperplasia •••••••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.2,3 Following oral administration, silodosin had a rapid onset of effect in men,3 with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose.6
Silodosin inhibited the human ether-a-go-go-related gene (HERG) tail current; however, it has weak cardiovascular effects.5 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.6
- Mechanism of action
The pathogenesis of benign prostatic hyperplasia is not fully understood: it is believed to involve several pathways, including inflammation, apoptosis, and cellular proliferation. Most drug therapies aim to alleviate symptoms of benign prostatic hyperplasia, silodosin included. Lower urinary tract symptoms of benign prostatic hyperplasia are categorized into three main groups: voiding or obstructive (hesitancy, slow stream, intermittency, incomplete emptying), storage or irritative (frequency, urgency, nocturia, urge urinary incontinence), and postmicturition (postvoid dribbling). Prostate contraction is the main contributor to lower urinary tract symptoms of benign prostatic hyperplasia. The smooth muscle tone of the prostate is regulated by α1A-adrenoceptors, which are the most highly expressed subtype of α1adrenoceptors in the human prostate tissue.2 It has been reported that blockade of α1A-adrenoceptors relieves bladder outlet obstruction. Blockade of α1D-adrenoceptors, another subtype found in prostate tissue, is believed to alleviate storage symptoms due to detrusor overactivity.6
α1-adrenoceptors are G protein-coupled receptors: upon binding of its natural ligand, norepinephrine and epinephrine, leads to the activation of phospholipase C and downstream signalling molecules, including inositol triphosphate and diacylglycerol. Ultimately, there is an increase in intracellular calcium levels and, consequently, smooth muscle contraction. Silodosin is an antagonist of α1-adrenoceptors, with the highest selectivity for the α1A-adrenoceptor subtype. By blocking the α1A-adrenoceptor signalling pathway, silodosin promotes prostatic and urethral smooth muscle relaxation, thereby improving lower urinary tract symptoms such as voiding. Silodosin also targets afferent nerves in the bladder, relieving bladder overactivity and storage symptoms.2
Target Actions Organism AAlpha-1A adrenergic receptor antagonistHumans AAlpha-1D adrenergic receptor antagonistHumans AAlpha-1B adrenergic receptor antagonistHumans UHERG human cardiac K+ channel blockerHumans - Absorption
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.7 Silodosin glucuronide or KMD-3213G, the main metabolite of silodosin, has an AUC three- or four fold higher than for the parent compound.2
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.7
- Volume of distribution
Silodosin has an apparent volume of distribution of 49.5 L.7
- Protein binding
Silodosin is approximately 97% protein bound.7
- Metabolism
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.7
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.4
Hover over products below to view reaction partners
- Route of elimination
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.7
- 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.7
- Clearance
After intravenous administration, the plasma clearance of silodosin was approximately 10 L/hour. 7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Oral LD50 is 800 mg/kg in rats.8
In clinical trials, postural hypotension was the most common dose-limiting adverse event. In case of drug overdose leading to hypotension, the patient should be placed in a supine position to restore blood pressure and normalize heart rate. Further measures, such as administration of intravenous fluids, may be initiated. In case of the use of vasopressors, renal function should be monitored and supported as needed. Since silodosin is highly bound to plasma proteins, dialysis is unlikely to be beneficial.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Silodosin can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Silodosin. Abrocitinib The excretion of Silodosin can be decreased when combined with Abrocitinib. Acebutolol The risk or severity of orthostatic hypotension and dizziness can be increased when Acebutolol is combined with Silodosin. Adagrasib The excretion of Silodosin can be decreased when combined with Adagrasib. - Food Interactions
- Take with food. A moderate fat or calorie meal decreases drug exposure as well as the risk of adverse effects.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Rapilif (Ipca Urosciences ) / Urief (Watson Pharmaceuticals Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rapaflo Capsule 8 mg/1 Oral Avera McKennan Hospital 2015-03-23 2017-05-24 US 
Rapaflo Capsule 8 mg/1 Oral Actavis Pharma, Inc. 2009-03-23 2020-02-29 US 
Rapaflo Capsule 8 mg/1 Oral Physicians Total Care, Inc. 2010-09-15 Not applicable US 
Rapaflo Capsule 8 mg Oral Allergan 2011-10-26 2022-11-11 Canada 
Rapaflo Capsule 4 mg/1 Oral Avera McKennan Hospital 2015-05-01 2017-05-24 US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ag-silodosin Capsule 8 mg Oral Angita Pharma Inc. Not applicable Not applicable Canada Ag-silodosin Capsule 4 mg Oral Angita Pharma Inc. Not applicable Not applicable Canada Apo-silodosin Capsule 4 mg Oral Apotex Corporation Not applicable Not applicable Canada Auro-silodosin Capsule 4 mg Oral Auro Pharma Inc 2022-02-16 Not applicable Canada Auro-silodosin Capsule 8 mg Oral Auro Pharma Inc 2022-02-16 Not applicable Canada
Categories
- ATC Codes
- G04CA04 — Silodosin
- Drug Categories
- Adrenergic Agents
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs Used in Benign Prostatic Hypertrophy
- Genito Urinary System and Sex Hormones
- Genitourinary Agents
- Heterocyclic Compounds, Fused-Ring
- Neurotransmitter Agents
- P-glycoprotein substrates
- Peripheral alpha-1 blockers
- Selective Alfa-1-adrenergic Blocking Agents
- UGT2B7 substrates
- Urological Agents
- Urologicals
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indolecarboxamides and derivatives. These are compounds containing a carboxamide group attached to an indole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indolecarboxylic acids and derivatives
- Direct Parent
- Indolecarboxamides and derivatives
- Alternative Parents
- Dialkylarylamines / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Aralkylamines / Vinylogous amides / 1,3-aminoalcohols / Amino acids and derivatives / Primary carboxylic acid amides / Dialkylamines show 7 more
- Substituents
- 1,3-aminoalcohol / Alcohol / Alkanolamine / Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound show 26 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- CUZ39LUY82
- CAS number
- 160970-54-7
- InChI Key
- PNCPYILNMDWPEY-QGZVFWFLSA-N
- InChI
- 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
- IUPAC Name
- 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide
- SMILES
- C[C@H](CC1=CC2=C(N(CCCO)CC2)C(=C1)C(N)=O)NCCOC1=CC=CC=C1OCC(F)(F)F
References
- General References
- Yoshida M, Homma Y, Kawabe K: Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. Expert Opin Investig Drugs. 2007 Dec;16(12):1955-65. [Article]
- Rossi M, Roumeguere T: Silodosin in the treatment of benign prostatic hyperplasia. Drug Des Devel Ther. 2010 Oct 27;4:291-7. doi: 10.2147/DDDT.S10428. [Article]
- Keating GM: Silodosin: a review of its use in the treatment of the signs and symptoms of benign prostatic hyperplasia. Drugs. 2015 Feb;75(2):207-17. doi: 10.1007/s40265-014-0344-z. [Article]
- Vishnuvardhan C, Baikadi S, Borkar RM, Srinivas R, Satheeshkumar N: In vivo metabolic investigation of silodosin using UHPLC-QTOF-MS/MS and in silico toxicological screening of its metabolites. J Mass Spectrom. 2016 Oct;51(10):867-882. doi: 10.1002/jms.3795. [Article]
- Tatemichi S, Kiguchi S, Kobayashi M, Yamazaki Y, Shibata N, Uruno T: Cardiovascular effects of the selective alphalA-adrenoceptor antagonist silodosin (KMD-3213), a drug for the treatment of voiding dysfunction. Arzneimittelforschung. 2006;56(10):682-7. doi: 10.1055/s-0031-1296773. [Article]
- Yamanishi T, Mizuno T, Kamai T, Yoshida K, Sakakibara R, Uchiyama T: Management of benign prostatic hyperplasia with silodosin. Open Access J Urol. 2009 Aug 20;1:1-7. doi: 10.2147/rru.s5004. [Article]
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
- Biosynth Carbosynth: Silodosin Safety Data Sheet [Link]
- Selleck Chemicals: Silodosin Safety Data Sheet [Link]
- External Links
- KEGG Drug
- D01965
- PubChem Compound
- 5312125
- PubChem Substance
- 175427058
- ChemSpider
- 4471557
- BindingDB
- 50160154
- 720825
- ChEBI
- 135929
- ChEMBL
- CHEMBL24778
- ZINC
- ZINC000003806063
- PharmGKB
- PA165291889
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Silodosin
- FDA label
- Download (846 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Benign Prostatic Hyperplasia (BPH) 3 somestatus stop reason just information to hide 4 Completed Treatment Benign Prostatic Hyperplasia (BPH) / Nocturia 1 somestatus stop reason just information to hide 4 Completed Treatment Benign Prostatic Hypertrophy 1 somestatus stop reason just information to hide 4 Completed Treatment Neurogenic Bladder / Voiding Dysfunction 1 somestatus stop reason just information to hide 4 Completed Treatment Ureteral Stones 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 8 mg/1 Capsule Oral Capsule Oral 4 mg/1 Capsule, gelatin coated Oral 4 mg/1 Capsule, gelatin coated Oral 8 mg/1 Capsule Oral 4 MG Capsule Oral 8 MG Capsule, coated Oral 8 mg Capsule, coated Oral 4 mg Tablet; tablet, film coated Oral 4 MG Tablet, film coated Oral 4 mg Tablet, coated Oral 4 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5403847 No 1995-04-04 2012-11-13 US US5387603 No 1995-02-07 2018-12-01 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 105 - 109°C FDA label water solubility <1 mg/mL Selleck Chemicals MSDS - Predicted Properties
Property Value Source Water Solubility 0.0111 mg/mL ALOGPS logP 2.96 ALOGPS logP 3.05 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 14.87 Chemaxon pKa (Strongest Basic) 9.66 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 97.05 Å2 Chemaxon Rotatable Bond Count 14 Chemaxon Refractivity 128.92 m3·mol-1 Chemaxon Polarizability 49.89 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.7383 Caco-2 permeable - 0.5847 P-glycoprotein substrate Substrate 0.8467 P-glycoprotein inhibitor I Non-inhibitor 0.5833 P-glycoprotein inhibitor II Inhibitor 0.7864 Renal organic cation transporter Non-inhibitor 0.7288 CYP450 2C9 substrate Non-substrate 0.8226 CYP450 2D6 substrate Non-substrate 0.6362 CYP450 3A4 substrate Substrate 0.6585 CYP450 1A2 substrate Non-inhibitor 0.7439 CYP450 2C9 inhibitor Non-inhibitor 0.7569 CYP450 2D6 inhibitor Non-inhibitor 0.5958 CYP450 2C19 inhibitor Non-inhibitor 0.5562 CYP450 3A4 inhibitor Inhibitor 0.7424 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5723 Ames test Non AMES toxic 0.6667 Carcinogenicity Non-carcinogens 0.8529 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4845 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.98 hERG inhibition (predictor II) Inhibitor 0.8366
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 202.44289 predictedDeepCCS 1.0 (2019) [M+H]+ 204.80089 predictedDeepCCS 1.0 (2019) [M+Na]+ 210.89406 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Lepor H, Hill LA: Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability. Pharmacotherapy. 2010 Dec;30(12):1303-12. doi: 10.1592/phco.30.12.1303. [Article]
- Yamada S, Kato Y, Okura T, Kagawa Y, Kawabe K: 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. Biol Pharm Bull. 2007 Jul;30(7):1237-41. [Article]
- Yamanishi T, Mizuno T, Kamai T, Yoshida K, Sakakibara R, Uchiyama T: Management of benign prostatic hyperplasia with silodosin. Open Access J Urol. 2009 Aug 20;1:1-7. doi: 10.2147/rru.s5004. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Yamanishi T, Mizuno T, Kamai T, Yoshida K, Sakakibara R, Uchiyama T: Management of benign prostatic hyperplasia with silodosin. Open Access J Urol. 2009 Aug 20;1:1-7. doi: 10.2147/rru.s5004. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- Lepor H, Hill LA: Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability. Pharmacotherapy. 2010 Dec;30(12):1303-12. doi: 10.1592/phco.30.12.1303. [Article]
- Sugawara T, Hirasawa A, Hashimoto K, Tsujimoto G: Differences in the subcellular localization of alpha1-adrenoceptor subtypes can affect the subtype selectivity of drugs in a study with the fluorescent ligand BODIPY FL-prazosin. Life Sci. 2002 Mar 22;70(18):2113-24. doi: 10.1016/s0024-3205(01)01533-8. [Article]
- Yamanishi T, Mizuno T, Kamai T, Yoshida K, Sakakibara R, Uchiyama T: Management of benign prostatic hyperplasia with silodosin. Open Access J Urol. 2009 Aug 20;1:1-7. doi: 10.2147/rru.s5004. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Blocker
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661)
- Specific Function
- C3hc4-type ring finger domain binding
Components:
| Name | UniProt ID |
|---|---|
| Potassium voltage-gated channel subfamily H member 2 | Q12809 |
| Potassium voltage-gated channel subfamily H member 6 | Q9H252 |
| Potassium voltage-gated channel subfamily H member 7 | Q9NS40 |
References
- Tatemichi S, Kiguchi S, Kobayashi M, Yamazaki Y, Shibata N, Uruno T: Cardiovascular effects of the selective alphalA-adrenoceptor antagonist silodosin (KMD-3213), a drug for the treatment of voiding dysfunction. Arzneimittelforschung. 2006;56(10):682-7. doi: 10.1055/s-0031-1296773. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- Glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage
- Specific Function
- Aldehyde dehydrogenase (nad+) activity
- Gene Name
- ALDH2
- Uniprot ID
- P05091
- Uniprot Name
- Aldehyde dehydrogenase, mitochondrial
- Molecular Weight
- 56380.93 Da
References
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:11306097, PubMed:18276838). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (PubMed:30538128). S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity)
- Specific Function
- Aldo-keto reductase (nadph) activity
- Gene Name
- AKR1A1
- Uniprot ID
- P14550
- Uniprot Name
- Aldo-keto reductase family 1 member A1
- Molecular Weight
- 36572.71 Da
References
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Matsubara Y, Kanazawa T, Kojima Y, Abe Y, Kobayashi K, Kanbe H, Harada H, Momose Y, Terakado S, Adachi Y, Midgley I: [Pharmacokinetics and disposition of silodosin (KMD-3213)]. Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45. [Article]
- Cantrell MA, Bream-Rouwenhorst HR, Hemerson P, Magera JS Jr: Silodosin for benign prostatic hyperplasia. Ann Pharmacother. 2010 Feb;44(2):302-10. doi: 10.1345/aph.1M320. Epub 2010 Jan 13. [Article]
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Matsubara Y, Kanazawa T, Kojima Y, Abe Y, Kobayashi K, Kanbe H, Harada H, Momose Y, Terakado S, Adachi Y, Midgley I: [Pharmacokinetics and disposition of silodosin (KMD-3213)]. Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45. [Article]
- FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:17523162, PubMed:21820390, PubMed:23468132, PubMed:24594635, PubMed:24723470, PubMed:24806754, PubMed:31873305, PubMed:7957936, PubMed:8898203, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:28012258, PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (By similarity)
- Specific Function
- Abc-type transporter activity
- Gene Name
- ABCB4
- Uniprot ID
- P21439
- Uniprot Name
- Phosphatidylcholine translocator ABCB4
- Molecular Weight
- 141521.845 Da
References
- Matsubara Y, Kanazawa T, Kojima Y, Abe Y, Kobayashi K, Kanbe H, Harada H, Momose Y, Terakado S, Adachi Y, Midgley I: [Pharmacokinetics and disposition of silodosin (KMD-3213)]. Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45. [Article]
Drug created at March 19, 2008 16:17 / Updated at April 23, 2024 11:38