HA15 是一种高效特异性的内质网伴侣蛋白BiP/GRP78/HSPA5抑制剂，可抑制 BiP 的 ATP 酶活性，具有抗肿瘤活性。
| 生物活性 | HA15 is a potent and specific inhibitor of ER chaperoneBiP/GRP78/HSPA5, inhibits the ATPase activity of BiP, with anti-cancerous activity[1]. |
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体外研究
(In Vitro) | HA15 (10 μM; 1-24 hours) induces an early endoplasmic reticulum stress (ER Stress)[1].
HA15 (0-10μM; 24 hours) decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50of 1-2.5 μM in A375 cells[1].
HA15 (1-10 μM; 24 hours) induces apoptosis in A375 cells[1].
HA15 (1-24 μM; 24 hours) induces autophagy[1].
HA15 (10 μM; 48 hours) has high efficiency in inducing cell death and ER stress in BRAF-inhibitor-resistant melanoma cells. And HA15 inhibits tumor growth through autophagic and apoptotic mechanisms initiated by ER stress[1].
No deleterious effects on the viability of normal human melanocytes or human fibroblasts were observed with low or high doses of HA15[1].
Cell Viability Assay[1] | Cell Line: | A375 cells | | Concentration: | 1 μM,2.5 μM,5 μM,7.5 μM,10 μM | | Incubation Time: | 24 hours | | Result: | Decreased melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO) in A375 cells. |
Apoptosis Analysis[1] | Cell Line: | A375 cells | | Concentration: | 1 μM, 5 μM, 10 μM | | Incubation Time: | 24 hours | | Result: | Induces apoptosis. |
Cell Autophagy Assay[1] | Cell Line: | A375 cells | | Concentration: | 1 μM, 4 μM, 10 μM, 24 μM | | Incubation Time: | 24 hours | | Result: | Increased LC3B-II expression after 1 hour and persisted after 24 hours, enhanced the expression level of Beclin 1, clearly be indicated that induces autophagy. |
Western Blot Analysis[1] | Cell Line: | A375 cells | | Concentration: | 10 μM | | Incubation Time: | 1 hour, 4 hours, 10 hours, 24 hours | | Result: | Exhibited a rapid induction within 1 hour of the ER stress markers (phosphorylation of PERK and elF2α and a weak increase in ATF4 and CHOP expression) |
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体内研究
(In Vivo) | HA15 (0.7 mg/mouse/day; i.h.; over 2 weeks) inhibits melanoma tumor development in mice, induces no apparent toxicity and no change in their behavior, body mass, or liver mass, suggesting an absence of hepatomegaly[1].
HA15 (0.7 mg/mouse; i.p.; 5 days/week) suppresses MPM tumor growth in vivo[3].
| Animal Model: | 6-weeks female BALB/c nu/nu (nude) mice with A375 melanoma cells xenograft[1] | | Dosage: | 0.7 mg/mouse/day | | Administration: | Subcutaneous injection; over a period of 2 weeks | | Result: | Attenuated the development of tumors. |
| Animal Model: | Mouse, NSG (NOD-scid IL2Rγnull)[3] | | Dosage: | 0.7 mg/mouse | | Administration: | Intraperitoneal injection, 5 days/week, for 5 weeks | | Result: | Suppressed MPM tumor growth. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(107.16 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.1433 mL | 10.7163 mL | 21.4326 mL | | 5 mM | 0.4287 mL | 2.1433 mL | 4.2865 mL | | 10 mM | 0.2143 mL | 1.0716 mL | 2.1433 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。-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: ≥ 2.5 mg/mL (5.36 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.36 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 *以上所有助溶剂都可在本网站选购。
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