SK1-I hydrochloride (BML-258 hydrochloride) 是鞘氨醇的类似物,是同功酶特异性SPHK1竞争抑制剂,Ki值为 10 μM。SK1-I hydrochloride 对 SPHK2,PKCα,PKCδ,PKA,AKT1,ERK1,EGFR,CDK2,IKKβ 或 CamK2β 无活性。SK1-I hydrochloride 增强自噬并具有抗肿瘤活性。
生物活性 | SK1-I hydrochloride (BML-258 hydrochloride), an analog of sphingosine, is an isozyme-specific competitiveSPHK1inhibitor with aKivalue of 10 μM[1]. SK1-I hydrochloride shows no activity atSPHK1PKCα,PKCδ,PKA,AKT1,ERK1,EGFR,CDK2, IKKβ or CamK2β. SK1-I hydrochloride enhancesautophagyand has antitumor activity[2]. |
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体外研究 (In Vitro) | SK1-I hydrochloride (0-10 μM; 24 hours) attenuates cancer cell growth and survival in a TP53-dependent manner in HCT116 cells and HCT116 cells bearingTP53null cancer[2]. SK1-I hydrochloride (0-20 μM; 12 hours) induces more CASP3 cleavage in HCT116 cells, compared to HCT116 cells lacking TP53, leading to a hallmark of apoptosis[2].
Cell Viability Assay[2] Cell Line: | HCT116 cells and HCT116 cells bearingTP53null cancer | Concentration: | 0 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM | Incubation Time: | 24 hours | Result: | Decreased cancer cell growth and survival. |
Western Blot Analysis[2] Cell Line: | HCT116 cells and HCT116 cells bearingTP53null cancer | Concentration: | 0 μM, 5 μM, 10 μM, 20 μM | Incubation Time: | 12 hours | Result: | Induced more CASP3 cleavage in HCT116 cells, compared to HCT116 cells lacking TP53. |
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体内研究 (In Vivo) | Pre-treatment with SK1-I hydrochloride (BML-258 hydrochloride; intraperitoneal (i.p.) injection; once; 24 hours prior to baseline mean arterial blood pressure (MAP) measurement; 75 mg/kg) before anandamide (i.v. injection; two doses; 1 and 10 mg/kg) significantly decreases the hypotensive response[3].
Animal Model: | Male C57BL/6 mice (24 ± 3.5 g)[3] | Dosage: | 75 mg/kg | Administration: | Intraperitoneal (i.p.) injection; once; 24 hours prior to baseline MAP measurement | Result: | Significantly lowered baseline mean arterial blood pressure (MAP). |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 250 mg/mL(796.53 mM;Need ultrasonic) 配制储备液 1 mM | 3.1861 mL | 15.9307 mL | 31.8613 mL | 5 mM | 0.6372 mL | 3.1861 mL | 6.3723 mL | 10 mM | 0.3186 mL | 1.5931 mL | 3.1861 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (6.63 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (6.63 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (6.63 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (6.63 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (6.63 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (6.63 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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