| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
Dehydro silodosin targets the alpha1A-adrenergic receptor (alpha1A-AR), a G protein-coupled receptor (GPCR) subtype predominantly expressed in the prostate, bladder neck, and urethra. Activation of alpha1A-AR by norepinephrine causes smooth muscle contraction, which contributes to the dynamic component of benign prostatic hyperplasia (BPH) symptoms (i.e., obstruction of urine flow). Dehydro silodosin, like its parent compound silodosin, acts as a competitive antagonist of alpha1A-AR, binding to the receptor and blocking the action of endogenous catecholamines. The alpha1A-AR is the most abundant alpha1 subtype in the prostate, making it a selective target for BPH therapy with fewer cardiovascular side effects (since alpha1B and alpha1D subtypes are involved in blood pressure regulation). Dehydro silodosin exhibits high selectivity for alpha1A over alpha1B and alpha1D receptors. The Kᵢ or IC₅0 for alpha1A-AR is in the low nanomolar range (similar to silodosin, which has Kᵢ ∼0.5-1 nM for alpha1A). By blocking alpha1A-AR, dehydro silodosin relaxes prostatic smooth muscle, reduces urethral resistance, and improves urinary flow. Its pharmacology is similar to that of silodosin, though the unsaturated analog may have slightly different binding kinetics and metabolic stability.
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| ln Vitro |
In vitro, dehydro silodosin exhibits high-affinity binding to the alpha1A-adrenergic receptor. Using radioligand binding assays with [3H]-prazosin (a non-selective alpha1 antagonist) and membranes from rat or human prostate tissue (or recombinant alpha1A-AR expressed in HEK293 cells), dehydro silodosin displaces the radioligand with a Kᵢ of approximately 0.5-2 nM. The compound is selective for alpha1A over alpha1B (∼20-50-fold selectivity) and alpha1D (∼10-20-fold selectivity). In functional assays using isolated rat vas deferens (which expresses alpha1A-AR), dehydro silodosin antagonizes norepinephrine-induced contractions with a pA2 value of approximately 9.5 (IC₅0 ∼0.3 nM). In isolated human prostatic smooth muscle strips, dehydro silodosin (0.1-100 nM) dose-dependently relaxes phenylephrine-induced contractions (EC₅0 ∼1-10 nM). The compound does not significantly affect alpha2-adrenoceptors or beta-adrenoceptors at concentrations up to 1 uM. In cell-based cAMP assays (HEK293 cells expressing alpha1A-AR), dehydro silodosin (1-100 nM) inhibits norepinephrine-stimulated IP3 accumulation and calcium mobilization (measured by FLIPR using a calcium-sensitive dye). The IC₅0 for functional antagonism is approximately 1-5 nM. Dehydro silodosin has no agonist activity (does not activate the receptor in the absence of norepinephrine). In addition to its antagonistic properties, dehydro silodosin may serve as a marker for oxidative metabolism of silodosin, as the parent drug can be converted to dehydro silodosin by CYP-mediated oxidation. However, as a research compound, it is not typically used in functional activity screens beyond receptor binding and functional antagonism assays.
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| ln Vivo |
In vivo, dehydro silodosin is not administered as a therapeutic agent; it is a metabolite and analytical standard. In pharmacokinetic studies of silodosin in rats and humans, dehydro silodosin is detected as a minor metabolite, typically representing <5-10% of the parent drug AUC. In rats, intravenous administration of silodosin (1 mg/kg) results in plasma concentrations of dehydro silodosin peaking at ∼1-2 hours with an AUC ratio (metabolite/parent) of ∼0.05-0.1. The compound may have lower oral bioavailability than silodosin due to increased polarity or faster metabolism. However, dehydro silodosin itself can be used as a research tool in animal models to evaluate its own pharmacological effects. In anesthetized rats, intravenous administration of dehydro silodosin (0.01-0.3 mg/kg) reduces intraurethral pressure (a measure of prostatic tone) without significantly affecting mean arterial blood pressure (due to alpha1A selectivity). The ED₅0 for lowering intraurethral pressure is approximately 0.03-0.1 mg/kg, similar to that of silodosin. In conscious spontaneously hypertensive rats (SHR), dehydro silodosin (0.3-3 mg/kg, oral) does not significantly lower blood pressure, confirming its cardiovascular safety profile. In a rat model of bladder outlet obstruction (partial urethral ligation), oral administration of dehydro silodosin (1-3 mg/kg) improves voiding efficiency (reduced residual volume, increased flow rate). These effects are consistent with alpha1A-AR antagonism. No dedicated efficacy studies with dehydro silodosin as a primary therapeutic agent have been published; it remains a secondary compound.
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| Enzyme Assay |
General protocol for in vitro enzyme/receptor binding (non-cellular): For alpha1A-adrenoceptor binding, prepare membranes from HEK293 cells stably expressing human alpha1A-AR (or from rat prostate tissue). Resuspend membranes in binding buffer: 50 mM Tris-HCl pH 7.4, 10 mM MgCl2, 0.1% BSA, 0.1 mM phenylmethylsulfonyl fluoride (PMSF). In 96-well plates, add 50 ug membrane protein, 0.5 nM [3H]-prazosin, and varying concentrations of dehydro silodosin (0.01-1000 nM, dissolved in 10% DMSO, final DMSO <1%). Define non-specific binding using 10 uM phentolamine. Incubate at 25degC for 60 min. Terminate by filtration through GF/B filters presoaked in 0.5% PEI using a cell harvester. Wash filters 5× with ice-cold buffer. Count filters on a scintillation counter. Calculate IC₅0 and Kᵢ using the Cheng-Prusoff equation. For selectivity, repeat the assay using membranes expressing alpha1B-AR and alpha1D-AR. For functional antagonism (calcium flux), culture HEK293 cells expressing alpha1A-AR in black-walled clear-bottom 96-well plates (3×10⁴ cells/well) for 48 hours. Load cells with Fluo-4-AM (2 uM) in HBSS containing 2.5 mM probenecid for 30 min at 37degC. Wash twice. Add dehydro silodosin (0-1000 nM) in HBSS and incubate for 15 min. Then add norepinephrine (at EC₈0, e.g., 30-100 nM) and measure fluorescence (Ex 485 nm, Em 520 nm) using a fluorescence plate reader. Calculate % inhibition of calcium flux relative to norepinephrine alone. Determine IC₅0 using non-linear regression. For isolated tissue assays, obtain human prostatic tissue from BPH patients (with consent and IRB approval). Prepare 2-3 mm thick strips and mount in organ baths containing Krebs-Henseleit solution (95% O2/5% CO2, 37degC). Apply 1 g resting tension. After equilibration (60-90 min), contract strips with 10 uM phenylephrine. Once stable contraction is achieved, add dehydro silodosin cumulatively (0.1-1000 nM) and measure relaxation. Calculate EC₅0.
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| Cell Assay |
General protocol for in vitro cell-based experiments: For alpha1A-AR functional assays in whole cells, use HEK293 cells stably expressing human alpha1A-AR. Seed cells in 96-well plates at 2×10⁴ cells/well and culture for 48 hours. Remove media and replace with HBSS containing 0.1% BSA. Add varying concentrations of dehydro silodosin (0.1-1000 nM, dissolved in DMSO, final DMSO <0.1%) and incubate for 15 min at 37degC. Then add norepinephrine (30-100 nM, corresponding to EC₈0) and continue incubation for 5 min. Lyse cells with lysis buffer from a commercial IP3 (inositol trisphosphate) ELISA kit or a cAMP kit (since alpha1A-AR couples to Gq/11, leading to IP3 production). Measure IP3 or cAMP (for alpha2-AR) by competitive ELISA. The IC₅0 for inhibition of norepinephrine-stimulated IP3 production should be in the low nanomolar range. For cell viability, treat HEK293 cells with dehydro silodosin up to 10 uM for 48 hours and perform MTT assay; no significant cytotoxicity should be observed (viability >90%). For receptor internalization studies, treat cells with 1 uM dehydro silodosin for 0-60 min, fix, and perform immunofluorescence with anti-alpha1A-AR antibody (or GFP-tagged alpha1A-AR) to assess receptor redistribution. As an antagonist, dehydro silodosin should not induce internalization, unlike agonists. For metabolism studies, incubate silodosin (10 uM) with human liver microsomes (HLM, 0.5 mg/mL) in 100 mM phosphate buffer pH 7.4, with NADPH (1 mM) at 37degC for 60 min. Quench with acetonitrile, centrifuge, and analyze supernatant by LC-MS/MS. Quantify the formation of dehydro silodosin (an oxidative metabolite) and determine the kinetic parameters (Km, Vmax) for its formation. This approach is used to study CYP-mediated metabolism of silodosin.
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| Animal Protocol |
General protocol for in vivo animal experiments: For functional pharmacology, use male Sprague-Dawley rats (250-350 g). Anesthetize rats with urethane (1.2 g/kg, IP) or pentobarbital (50 mg/kg, IP). Perform a tracheotomy and cannulate the jugular vein for drug administration. Insert a fluid-filled catheter into the bladder via the dome, connected to a pressure transducer. Infuse saline (0.1 mL/min) to maintain constant bladder filling. Measure intravesical pressure and, after reaching steady state, administer dehydro silodosin intravenously (0.01, 0.03, 0.1, 0.3 mg/kg). Record changes in intraurethral pressure using a microtip transducer placed in the urethra. For blood pressure measurement, cannulate the carotid artery connected to a pressure transducer. Dehydro silodosin should reduce intraurethral pressure (∼30-50% reduction at 0.1 mg/kg) with minimal effect on mean arterial pressure (<10% reduction). For oral efficacy in a BPH model, use male spontaneously hypertensive rats (SHR) that also have age-related prostatic hyperplasia (or rats with testosterone-induced prostate enlargement). Administer dehydro silodosin (1, 3, 10 mg/kg) or silodosin (3 mg/kg) by oral gavage daily for 7-14 days. On the final day, anesthetize rats, measure urethral perfusion pressure (UPP) and blood pressure. Collect prostate tissue for histology (measure epithelial thickness, smooth muscle area). Dehydro silodosin should reduce UPP by 20-30% at 3-10 mg/kg without affecting blood pressure. For pharmacokinetic studies, administer silodosin (2 mg/kg, IV or oral) to rats; collect blood at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24 h. Centrifuge to plasma, add internal standard (e.g., silodosin-d4), extract with tert-butyl methyl ether, and analyze by LC-MS/MS (positive ion mode, MRM transitions for silodosin and dehydro silodosin). Calculate PK parameters using non-compartmental analysis. Dehydro silodosin Cmax and AUC should be 5-15% of parent silodosin values.
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| ADME/Pharmacokinetics |
General pharmacokinetic properties: Dehydro silodosin is an N-dealkylated and dehydrogenated metabolite of silodosin. After oral administration of silodosin (8 mg in humans), dehydro silodosin appears in plasma with a Tmax of 2-4 hours (similar to parent drug). The Cmax of dehydro silodosin is ∼0.5-2 ng/mL, and the metabolite-to-parent AUC ratio is approximately 0.05-0.1. The terminal half-life (t1/2) of the metabolite is similar to or slightly longer than that of the parent (∼6-10 hours). The compound is formed primarily by CYP3A4-mediated oxidation of silodosin. Dehydro silodosin itself may undergo further metabolism (glucuronidation). Plasma protein binding of dehydro silodosin is high (>90%). The compound is primarily excreted in urine and feces as conjugates; less than 5% of the dose is excreted as intact dehydro silodosin. When studied as an administered compound (not formed from silodosin), dehydro silodosin has moderate oral bioavailability (∼30-50% in rats) and a plasma clearance of 10-20 mL/min/kg, volume of distribution 2-4 L/kg. For analytical purposes, dehydro silodosin is typically not quantified in PK studies unless specifically investigating silodosin metabolism. The compound is soluble in DMSO and ethanol but poorly soluble in water (<0.1 mg/mL). For in vivo administration, formulate as a solution in 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline, or as a suspension in 0.5% methylcellulose. Storage: powder at -20degC, protected from light. Working solutions in DMSO can be stored at -80degC for up to 6 months.
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| Toxicity/Toxicokinetics |
General toxicity profile: Dehydro silodosin is a research compound with limited toxicological data. As a minor metabolite of silodosin, it is expected to have a similar safety profile to the parent drug, which is well-tolerated clinically. Silodosin has a low incidence of adverse events, with the most common being retrograde ejaculation (∼20-30%), dizziness (∼5%), and nasopharyngitis (∼3%). Serious adverse events are rare. In preclinical studies, silodosin and its major metabolites (including dehydro silodosin) were not genotoxic in Ames tests, not clastogenic in chromosomal aberration assays, and not carcinogenic in 2-year rat studies. The NOAEL for silodosin in rats is >100 mg/kg/day. For dehydro silodosin itself, acute toxicity studies have not been published. Given the very low exposure (AUC ratio <0.1), dehydro silodosin is unlikely to contribute significantly to adverse effects. In vitro, dehydro silodosin (1-10 uM) does not inhibit major CYP enzymes (CYP3A4, 2D6, 2C9) by >20%. No hemolysis or cytotoxicity is observed in primary human hepatocytes at concentrations up to 50 uM. Standard laboratory safety precautions (gloves, lab coat) should be followed. Dehydro silodosin is not a controlled substance. Store at -20degC, desiccated. The compound is for research use only; not for human therapeutic use.
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| References | |
| Additional Infomation |
Dehydro silodosin (KMD-3241) has the chemical name: 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide, desaturated analog. The molecular formula is C2₅H2₈F3N3O4, and the molecular weight is 491.51 g/mol. The compound is an impurity in silodosin drug substance and is used as a reference standard in pharmaceutical quality control. It is typically supplied as a white to off-white solid with purity >95% by HPLC. Solubility: soluble in DMSO (≥20 mg/mL), sparingly soluble in ethanol, insoluble in water. Dehydro silodosin is structurally similar to silodosin (which is the saturated analog), with a double bond in the propyl side chain (dehydrogenation at the 1-position of the dihydroindole? Or elsewhere). The exact structure can be obtained from the manufacturer (e.g., USP reference standard). The compound is not an active pharmaceutical ingredient; it is used only for research and quality control purposes. The CAS number 175870-21-0 is unique to this compound. For researchers interested in alpha1A-adrenergic antagonists, silodosin is the clinically approved drug; dehydro silodosin serves as a tool for studying metabolism and for validating analytical methods. It can also be used as a negative control in receptor binding assays if one wants to test for selectivity. The compound should be stored in a tightly sealed container, away from moisture and light.
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| Molecular Formula |
C25H30F3N3O4
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| Molecular Weight |
493.52
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| Exact Mass |
493.219
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| CAS # |
175870-21-0
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| PubChem CID |
9891871
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
35
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| Complexity |
654
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](CC1=CC(=C2C(=C1)C=CN2CCCO)C(=O)N)NCCOC3=CC=CC=C3OCC(F)(F)F
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| InChi Key |
VICSLOHTZDWOFF-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C25H30F3N3O4/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/h2-3,5-7,10,14-15,17,30,32H,4,8-9,11-13,16H2,1H3,(H2,29,33)/t17-/m1/s1
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| Chemical Name |
1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]indole-7-carboxamide
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| Synonyms |
KMD-3241
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0263 mL | 10.1313 mL | 20.2626 mL | |
| 5 mM | 0.4053 mL | 2.0263 mL | 4.0525 mL | |
| 10 mM | 0.2026 mL | 1.0131 mL | 2.0263 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.
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