HA15
目录号 : GC19188
HA15是一种特异性靶向BiP/GRP78/HSPA5的分子，可结合并抑制其ATPase活性，导致BiP与PERK、IRE1α和ATF6分离，从而引发内质网应激。
Cas No.:1609402-14-3
Sample solution is provided at 25 µL, 10mM.
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HA15 is a molecule that specifically targets BiP/GRP78/HSPA5, binding to and inhibiting its ATPase activity, which leads to the dissociation of BiP from PERK, IRE1α, and ATF6, thereby triggering endoplasmic reticulum stress[1][2][3]. HA15 has demonstrated anti-tumor effects in a variety of human cancers, including melanoma, breast, pancreas, and adrenocortical carcinoma[2].
HA15 (1-10μM, 24h) decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50 of 1-2.5μM in A375 cells[1]. HA15 (10μM, 48h) induces typical dilated endoplasmic reticulum cisternae in A375 cells[1]. HA15 (1, 5 and 10μM; 48h) induces apoptosis in A375 cells by increasing the levels of the cleaved and activated form of caspase 9 and decreasing the levels of the zymogenic form of caspase 3[1].
HA15 (0.7mg/mouse, 5 days/week, 5 weeks, i.p.) treatment delayed tumor growth in malignant pleural mesothelioma (MPM) mouse model[2]. HA15 (0.5mg/kg twice weekly, 3 weeks, i.p.) in combination with BTZ, was more effective at inhibiting tumor growth than BTZ alone in a multiple myeloma mouse model[4].
References:
[1] Cerezo M, Lehraiki A, Millet A, et al. Compounds Triggering ER Stress Exert Anti-Melanoma Effects and Overcome BRAF Inhibitor Resistance. Cancer Cell. 2016 Jun 13;29(6):805-819.
[2] Xu D, Yang H, Yang Z, et al. Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma. Cancers (Basel). 2019 Oct 8;11(10):1502.
[3] Ruggiero C, Doghman-Bouguerra M, Ronco C, et al. The GRP78/BiP inhibitor HA15 synergizes with mitotane action against adrenocortical carcinoma cells through convergent activation of ER stress pathways. Mol Cell Endocrinol. 2018 Oct 15;474:57-64.
[4] Chen Y, Tao Y, Hu K, et al. GRP78 inhibitor HA15 increases the effect of Bortezomib on eradicating multiple myeloma cells through triggering endoplasmic reticulum stress. Heliyon. 2023 Sep 2;9(9):e19806.
HA15是一种特异性靶向BiP/GRP78/HSPA5的分子，可结合并抑制其ATPase活性，导致BiP与PERK、IRE1α和ATF6分离，从而引发内质网应激[1][2][3]。HA15已证明对多种人类癌症具有抗肿瘤作用，包括黑色素瘤、乳腺癌、胰腺癌和肾上腺皮质癌[2]。
与对照条件（DMSO）相比，HA15（1-10μM，24h）以剂量依赖性方式降低黑色素瘤细胞活力，在A375细胞中的IC50为1-2.5μM[1]。HA15（10μM，48h）诱导A375细胞中典型的扩张内质网池[1]。HA15（1、5和10μM，48小时）通过增加caspase 9的裂解和活化形式水平并降低caspase 3的酶原形式水平来诱导A375细胞凋亡[1]。
HA15（0.7mg/只小鼠，每周5天，5周，腹腔注射）治疗可延缓恶性胸膜间皮瘤（MPM）小鼠模型中的肿瘤生长[2]。HA15（0.5mg/kg，每周两次，3周，腹腔注射）与BTZ联合使用，在多发性骨髓瘤小鼠模型中抑制肿瘤生长的效果比单独使用BTZ更好[4]。
| Cell experiment [1]: | |
Cell lines | Resistant melanoma cell lines A375 |
Preparation Method | A375 cells were treated with indicated concentrations (1-10μM) of HA15. After 24h, viable cells were counted using the trypan blue dye exclusion method. For trypan blue staining, 200μl of cells was aseptically transferred to a 1.5ml clear Eppendorf tube and incubated for 3min at room temperature with an equal volume of 0.4% trypan blue solution. Viable cells were counted and the results are expressed as the percentage of the value of control cells. |
Reaction Conditions | 1-10μM, 24h |
Applications | HA15 decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50 of 1-2.5μM in A375 cells. |
| Animal experiment [2]: | |
Animal models | Malignant pleural mesothelioma (MPM) mouse model |
Preparation Method | Suspensions of tumor cells (in PBS) mixed with 1:1 with BD Matrigel Basement Membrane Matrix were subcutaneously inoculated in left and right flanks (BE261T cells: 1×106/injection). When tumors were palpable, mice were randomly assigned to treatment groups: (1) control; (2) Cisplatin (3.75mg/kg) plus Pemetrexed (83mg/kg) (i.p., once weekly) for five weeks; (3) HA15 (0.7mg/mouse, i.p., 5 days/week) for five weeks. Mice weight and tumor size were measured every three days. Tumor size was calculated as follows: (length × width × width)/2. At the endpoint, blood samples were collected through cardiac puncta and subjected to the determination of transaminase activities. |
Dosage form | 0.7mg/mouse, 5 days/week, 5 weeks, i.p. |
Applications | HA15 treatment delayed tumor growth in patient-derived xenograft models compared to the vehicle treatment. |
References: | |
| Cas No. | 1609402-14-3 | SDF | |
| Canonical SMILES | CC(NC1=NC(C2=CC=CC(NS(=O)(C3=C4C=CC=C(N(C)C)C4=CC=C3)=O)=C2)=CS1)=O | ||
| 分子式 | C23H22N4O3S2 | 分子量 | 466.58 |
| 溶解度 | DMSO : ≥ 50 mg/mL (107.16 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
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