SKF 96365 hydrochloride
(Synonyms: 1-[2-(4-甲氧基)-2-[3-(4-甲氧基苯基)丙氧基]乙基]咪唑) 目录号 : GC14641
SKF 96365 hydrochloride是一种具有口服活性的TRP通道/钙库操控性钙内流（SOCE）抑制剂，可阻断TRPC通道、电压门控钙通道及多种钾通道，并抑制STIM1介导的钙信号。
Cas No.:130495-35-1
Sample solution is provided at 25 µL, 10mM.
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SKF 96365 hydrochloride is an orally active TRP-channel/store-operated Ca²⁺ entry (SOCE) inhibitor that blocks TRPC channels, voltage-gated Ca²⁺ channels and multiple K⁺ channels, and suppresses STIM1-mediated Ca²⁺ signaling[1][2]. SKF 96365 hydrochloride is commonly used to investigate calcium homeostasis, cardiac arrhythmias and anti-tumor mechanisms[3].
In vitro, SKF 96365 hydrochloride (5-20µM; 48h) suppressed cell proliferation, arrested cells in G0/G1, reduced CD69/CD25 expression, collapsed mitochondrial membrane potential, opened the permeability-transition pore and markedly decreased IFN-γ, TNF-α and IL-10 secretion in mouse lymphocytes[4]. SKF 96365 hydrochloride (1-10µM; 6min) blocks native cardiac INa in rat ventricular myocytes with IC50=1.36µM (0.5Hz), shifts inactivation by -9.5mV, accelerates closed-state inactivation and slows recovery[5].
In vivo, SKF 96365 hydrochloride (100µg in 20µL; 5min; s.c.) reversed melittin-induced persistent spontaneous nociception, thermal hyperalgesia and mechanical hypersensitivity in the ipsilateral hindpaw of adult Sprague–Dawley rats[6]. SKF 96365 hydrochloride (20mg/kg/day; i.p.; 14 days) markedly reduced HCT116 xenograft tumor volume and weight, decreased p-CaMKIIγ/p-AKT and PCNA, and increased cleaved caspase-3/caspase-9 and LC3-II in BALB/c nude mice[7].
References:
[1] Liu H, Yang L, Chen KH, et al. SKF-96365 blocks human ether-à-go-go-related gene potassium channels stably expressed in HEK 293 cells. Pharmacol Res. 2016;104:61-69.
[2] Chen T, Zhu J, Zhang C, Huo K, Fei Z, Jiang XF. Protective effects of SKF-96365, a non-specific inhibitor of SOCE, against MPP+-induced cytotoxicity in PC12 cells: potential role of Homer1. PLoS One. 2013;8(1):e55601.
[3] Chen YF, Shen MR. The Important Role of Ion Transport System in Cervical Cancer. Int J Mol Sci. 2021;23(1):333.
[4] Ye Y, Zhang Y, Lu X, et al. The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin. Immunobiology. 2011;216(9):1044-1053.
[5] Chen KH, Liu H, Yang L, Jin MW, Li GR. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes. Pflugers Arch. 2015;467(6):1227-1236.
[6] Ding J, Zhang JR, Wang Y, et al. Effects of a non-selective TRPC channel blocker, SKF-96365, on melittin-induced spontaneous persistent nociception and inflammatory pain hypersensitivity. Neurosci Bull. 2012;28(2):173-181.
[7] Jing Z, Sui X, Yao J, et al. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway. Cancer Lett. 2016;372(2):226-238.
SKF 96365 hydrochloride是一种具有口服活性的TRP通道/钙库操控性钙内流（SOCE）抑制剂，可阻断TRPC通道、电压门控钙通道及多种钾通道，并抑制STIM1介导的钙信号[1][2]。SKF 96365 hydrochloride常用于研究钙稳态、心律失常及抗肿瘤机制[3]。
体外实验中，SKF 96365 hydrochloride（5-20µM；48h）可抑制小鼠淋巴细胞增殖，诱导G0/G1期阻滞，降低CD69/CD25表达，破坏线粒体膜电位，开放通透性转换孔，并显著减少IFN-γ、TNF-α和IL-10的分泌[4]。SKF 96365 hydrochloride（1-10µM；6min）可阻断大鼠心室肌细胞中的原生心脏INa，IC50为1.36µM（0.5Hz），使失活电位负移9.5mV，加速关闭态失活并延缓恢复[5]。
体内实验中，SKF 96365 hydrochloride（100µg in 20µL；5min；皮下注射）可逆转成年Sprague-Dawley大鼠同侧后爪中蜂毒肽诱导的持续自发性痛觉、热痛觉过敏和机械性过敏[6]。SKF 96365 hydrochloride（20mg/kg/天；腹腔注射；14天）显著减少BALB/c裸鼠中HCT116异种移植瘤的体积和重量，降低p-CaMKIIγ/p-AKT和PCNA表达，并增加cleaved caspase-3/caspase-9和LC3-II表达 [7]。
| Cell experiment [1]: | |
Cell lines | mouse lymphocytes |
Preparation Method | Lymph nodes were isolated from BALB/c mice and a singlecell suspension was prepared by passing the tissue through a 200µm nylon mesh screen. The cells were washed twice with PBS, counted and resuspended in RPMI-1640 medium containing 10% FBS, 100U/ml penicillin, 100µg/ml streptomycin, 2mM L-glutamine and 50µM 2-mercaptoethanol (complete medium). Lymphocytes at a density of 3×106/mL were added in a 96-well plate (200µL/well) and incubated at 37℃ in a humidified atmosphere of 5% CO2. Then cells were treated with different concentrations(5-20µM) of SKF 96365 hydrochloride, and were then cultured for 48h. MTT assay was used for cell proliferation detection. Cell cycle propagation, as determined by DNA ploidy, was assessed on the basis of PI incorporation. |
Reaction Conditions | 5-20µM; 48h |
Applications | SKF 96365 hydrochloride suppressed cell proliferation, arrested cells in G0/G1 in mouse lymphocytes. |
| Animal experiment [2]: | |
Animal models | Male albino Sprague-Dawley rats |
Preparation Method | Male albino Sprague-Dawley rats (weighing 180–220g) were housed in plastic cages with food and water ad libitum under a 12h:12h light/dark cycle at room temperature. The rats were acclimated to test boxes for 5 days (>30min per day) before the behavioral measurements. At the end of the experiments, all rats were sacrificed with an overdose of pentobarbital sodium (100mg/kg, i.p.). A volume of 50µL melittin solution (50µg dissolved in 50µL 0.9% sterile saline) was used for all experiments. SKF 96365 hydrochloride was dissolved in 0.9% sterile saline. To evaluate the effects of SKF 96365 hydrochloride on the induction and maintenance of persistent spontaneous nociception, one dose of SKF 96365 hydrochloride (100µg in 20µL) was administered 5min before s.c. melittin. The paw withdrawal thermal latency (PWTL, s) and paw withdrawal mechanical threshold (PWMT, g) measurements were made 2h after melittin injection. In addition, the baseline values of PWTL and PWMT in each group were measured prior to any treatment. In general, the experimental order of these two measurements was randomized to rule out the effects of test order. The experimenters were blind to the treatment. |
Dosage form | 100µg in 20µL; 5min; s.c. |
Applications | SKF 96365 hydrochloride reversed melittin-induced persistent spontaneous nociception in the ipsilateral hindpaw of adult Sprague–Dawley rats. |
References: | |
| Cas No. | 130495-35-1 | SDF | |
| 别名 | 1-[2-(4-甲氧基)-2-[3-(4-甲氧基苯基)丙氧基]乙基]咪唑 | ||
| 化学名 | (S)-1-(2-(4-methoxyphenyl)-2-(3-(4-methoxyphenyl)propoxy)ethyl)-1H-imidazole hydrochloride | ||
| Canonical SMILES | COC1=CC=C(C=C1)[C@@H](CN2C=CN=C2)OCCCC(C=C3)=CC=C3OC.Cl | ||
| 分子式 | C22H26N2O3.HCl | 分子量 | 402.92 |
| 溶解度 | ≥ 40.3mg/mL in DMSO | 储存条件 | 4°C, protect from light, stored under nitrogen |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4819 mL | 12.4094 mL | 24.8188 mL |
| 5 mM | 496.4 μL | 2.4819 mL | 4.9638 mL |
| 10 mM | 248.2 μL | 1.2409 mL | 2.4819 mL |
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动物数量 | 只 |
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Quality Control & SDS
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- Purity: >99.50%
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