Silodosin

SKU: orb1226063

Description

A highly potent, uroselective α1a-adrenoceptor antagonist with Ki of 36 pM; displays 583- and 56-fold lower potency against α1b and α1d respectors, respectively; inhibits norepinephrine-induced increases intracellular Ca2+ concentrations in CHO cells with IC50 of 0.32 nM; inhibits intraurethral pressure (IUP) response in vivo.Other Indication Approved(In Vitro):Silodosin (KAD 3213; KMD 3213) inhibits norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs.Silodosin potently inhibits 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but has 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively.Silodosin (0-10 μM; 24 hours) decreases ELK1 gene expression as a dose-dependent manner in all the bladder cancer cell lines.Silodosin (0-10 μM; 24 hours) decreases ELK1 protein expression as a as a dose-dependent manner.Silodosin (0-10 μM; 96 hours) insignificantly changes cell viability of AR-positive UMUC3 or TCCSUP cultured in an androgen-depleted condition or that of AR-negative 647V. In contrast, silodosin reduced the growth of UMUC3 cells cultured with normal FBS containing androgens (58% decrease at 10 μM).(In Vivo):Silodosin (intravenous injection; 0.1-0.3mg/kg) reduces the obstruction-induced increases in MinP by 27.7 % (0.1 mg/kg) and 20.8 %(0.3 mg/kg). It improves detrusor overactivity and reduces the grade of obstruction, and thus may be effective for both storage and voiding dysfunction for the treatment of LUTS/BPH.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 160970-54-7
• MW: 495.5345
• Purity: >98% (HPLC)
• Formula: C₂₅H₃₂F₃N₃O₄
• SMILES: O=C(C1=CC(C[C@H](NCCOC2=CC=CC=C2OCC(F)(F)F)C)=CC3=C1N(CCCO)CC3)N
• Target: Adrenergic Receptor
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Silodosin (intravenous injection; 0.1-0.3 mg/kg) reduces the obstruction-induced increases in MinP by 27.7 % (0.1 mg/kg) and 20.8 %(0.3 mg/kg). It improves detrusor overactivity and reduces the grade of obstruction, and thus may be effective for both storage and voiding dysfunction for the treatment of LUTS/BPH. Animal model: Sprague Dawley rats. Dosage: 0.1-0.3 mg/kg. Administration: Intravenous injection. Result: Effectively reduced contractions of both human and rat isolated ureters.
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• In Vitro:
  Silodosin (KAD 3213; KMD 3213) inhibits norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs. Silodosin potently inhibits 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but has 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. Silodosin (0-10 μM; 24 hours) decreases ELK1 gene expression as a dose-dependent manner in all the bladder cancer cell lines. Silodosin (0-10 μM; 24 hours) decreases ELK1 protein expression as a as a dose-dependent manner. Silodosin (0-10 μM; 96 hours) insignificantly changes cell viability of AR-positive UMUC3or TCCSUP cultured in an androgen-depleted condition or that of AR-negative 647V. In contrast, silodosin reduced the growth of UMUC3 cells cultured with normal FBS containing androgens (58% decrease at 10 μM). RT-PCR 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. Western blot analysis. 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. Cell Proliferation Assay Cell line: UMUC3, TCCSUP or AR-negative 647V cells. Concentration: 0.1, 0.5, 3.0, or 10 μM Incubation time: 96 hours. Result: Decreased cell viability of UMUC3 cells cultured with normal FBS containing androgens (58% decrease).
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

KAD 3213 | KMD 3213

Quick Database Links

Gene Symbol

Adrenergic Receptor