Siramesine hydrochloride |
رقم الكتالوجGC15222
One-Click Copy Product Info
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هيدروكلوريد Siramesine (Lu 28-179) هو ناهض قوي لمستقبلات Sigma-2يحتوي هيدروكلوريد Siramesine على تقارب شبه ناني لمستقبلات sigma-2 (IC = 0.12 نانومتر) ويعرض انتقائية 140 ضعفًا لمستقبلات sigma-2 على مستقبلات sigma-1 (IC50 = 17 نانومتر)يتسبب هيدروكلوريد السيراميسين في موت الخلايا من خلال زعزعة استقرار الميتوكوندريا ، ولكن ليس الجسيمات الحالةنشاط مضاد للسرطان
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 224177-60-0
Sample solution is provided at 25 µL, 10mM.
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Siramesine hydrochloride is an effective sigma-2 receptor agonist. Siramesine has an annanometer-level affinity for the sigma-2 receptor (IC50 = 0.12nM), and its selectivity for the sigma-2 receptor is 140 times that of the sigma-1 receptor (IC50 = 17nM) [1]. The sigma-2 receptor is highly expressed in various rapidly proliferating cancer cells and is considered a biomarker of cancer cells [2]. Siramesine triggers cell death through mitochondrial instability rather than lysosomes, showing effective anti-cancer activity [3].
In vitro, Siramesine (0-15μM) treatment of cultures containing glioblastoma stem cell-like spheres (GSS) for 24 hours reduced sphere formation, indicating its inhibitory effect on tumor stem cell properties [4]. The lysosomal destabilizing drug Siramesine (with a concentration higher than 20μM) can induce rapid cell death in many cell lines. In HaCaT cells, the concentration of Siramesine that induces significant cell death within 8 hours is within the range of 20-30μM, and 90% of the cells die after treatment with a concentration of 40-50μM of Siramesine. And Siramesine at concentrations greater than 25μM reduces the mitochondrial membrane potential (MMP) of HaCaT cells within 15 minutes [1].
In vivo, In C57 mice with cocaine-enhanced behavior, the sigma-2 receptor agonist Siramesine (0.1, 0.3, and 1mg/kg/d; i.p.) significantly reduced the dopamine release induced by cocaine in the striatum of freely moving mice, which may have therapeutic potential for treating cocaine relapse [5]. 24 hours before the test, Siramesine (1mg/kg/d; i.p.) combined with MEM (as well as AMA) administration could shorten the immobility time of rats. The combined treatment of Siramesine and AMA is not affected by progesterone nor by BD 1047 (a new sigma antagonist with preferential affinity for the sigma 1 site) [6].
References:
[1] Česen MH, Repnik U, Turk V, Turk B. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Cell Death Dis. 2013 Oct 3;4(10):e818.
[2] Huang Y S, Lu H L, Zhang L J, et al. Sigma‐2 receptor ligands and their perspectives in cancer diagnosis and therapy[J]. Medicinal research reviews, 2014, 34(3): 532-566.
[3] Bhatti I. The lysosomotropic agent siramesine induces cell death in prostate cancer cells and synergizes with the tyrosine kinase inhibitor lapatinib[J]. 2024.
[4] Jensen S S, Petterson S A, Halle B, et al. Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo[J]. BMC cancer, 2017, 17: 1-16.
[5] Klawonn AM, Nilsson A, Rådberg CF, Lindström SH, Ericson M, Granseth B, Engblom D, Fritz M. The Sigma-2 Receptor Selective Agonist Siramesine (Lu 28-179) Decreases Cocaine-Reinforced Pavlovian Learning and Alters Glutamatergic and Dopaminergic Input to the Striatum. Front Pharmacol. 2017 Oct 10;8:714.
[6] Skuza G, et al. The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats. J Physiol Pharmacol. 2006 Jun;57(2):217-29.
| Cell experiment [1]: | |
Cell lines | HaCaT cell |
Preparation Method | Cells were plated onto a 24-well plate at 0.5 × 105 cells per well and grown overnight before the experiment. Siramesine was dissolved in DMSO to make a 20mM stock solution, which was then diluted in complete culture medium to the final concentrations used. Inhibitors and antioxidants were applied 2 hours before the Siramesine treatment. After the cells were incubated with the diluted celecoxib for 8 hours, cell viability, cysteine aspartic acid protease activity, and cathepsin activity were measured. The integrity of lysosomal and mitochondrial membranes was determined by flow cytometry. |
Reaction Conditions | 5–40μM; 8 hours |
Applications | Siramesine can induce rapid cell death in a number of cell lines at concentrations above 20μM. In HaCaT cells, cell death was accompanied by caspase activation, rapid loss of mitochondrial membrane potential (MMP), cytochrome c release, cardiolipin peroxidation and typical apoptotic morphology. |
| Animal experiment [2]: | |
Animal models | C57/bl6 mice |
Preparation Method | Examined the effect of the sigma-2 receptor agonist Siramesine on cocaine-associated locomotion, Pavlovian learning, and reward neurocircuitry using electrophysiology recordings and in vivomicrodialysis. |
Dosage form | 0.1, 0.3, and 1mg/kg/day for 3 days; i.p. |
Applications | Via in vivomicrodialysis, Siramesine significantly decreased cocaine-evoked dopamine release in the striatum of freely moving mice. |
References: | |
| Cas No. | 224177-60-0 | SDF | |
| Chemical Name | 1'-(4-(1-(4-fluorophenyl)-1H-indol-3-yl)butyl)-3H-spiro[isobenzofuran-1,4'-piperidine] hydrochloride | ||
| Canonical SMILES | FC1=CC=C(N2C=C(C3=CC=CC=C32)CCCCN4CCC5(C6=CC=CC=C6CO5)CC4)C=C1.Cl | ||
| Formula | C30H32ClFN2O | M.Wt | 491.04 |
| الذوبان | >49.1mg/mL in DMSO | Storage | Desiccate at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0365 mL | 10.1825 mL | 20.3649 mL |
| 5 mM | 407.3 μL | 2.0365 mL | 4.073 mL |
| 10 mM | 203.6 μL | 1.0182 mL | 2.0365 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)