AT13387是一种小分子非安沙霉素类HSP90（热休克蛋白90）抑制剂，其作用机制是通过靶向AKT和ERK信号通路。
Cas No.:912999-49-6
Sample solution is provided at 25 µL, 10mM.
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AT13387 is a small-molecule, non-ansamycin HSP90 (heat shock protein 90) inhibitor that acts by targeting the AKT and ERK signaling pathways[1]. AT13387 inhibits tumor cell growth and migration and exerts synergistic anti-cancer effects when combined with radiotherapy[2]. AT13387 is commonly used in the study of non-small cell lung cancer (NSCLC)[3].
AT13387 (0.1 - 2.5µM, 72h) inhibited cell proliferation in glioblastoma cell lines in a dose-dependent manner (IC50 ≤ 0.25μM). AT13387 (0.4µM, 24h) significantly inhibited the proliferation and angiogenic potential of glioma cells[4].
AT13387 (5, 10mg/kg/day; 3 days; i.p.) significantly reduced tumor growth and prolonged both median and overall survival in the radiosensitive HCT116 human adenocarcinoma xenograft mouse model[2].
References:
[1] Riess J W, Reckamp K L, Frankel P, et al. Erlotinib and onalespib lactate focused on EGFR exon 20 insertion non-small cell lung cancer (NSCLC): a California Cancer Consortium Phase I/II Trial (NCI 9878)[J]. Clinical lung cancer, 2021, 22(6): 541-548.
[2] Spiegelberg D, Abramenkovs A, Mortensen A C L, et al. The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach[J]. Scientific Reports, 2020, 10(1): 5923.
[3] Mooradian M J, Cleary J M, Giobbie‐Hurder A, et al. Dose‐escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF‐mutant solid tumors[J]. Cancer, 2023, 129(12): 1904-1918.
[4] Canella A, Welker A M, Yoo J Y, et al. Efficacy of onalespib, a long-acting second-generation HSP90 inhibitor, as a single agent and in combination with temozolomide against malignant gliomas[J]. Clinical Cancer Research, 2017, 23(20): 6215-6226.
AT13387是一种小分子非安沙霉素类HSP90（热休克蛋白90）抑制剂，其作用机制是通过靶向AKT和ERK信号通路[1]。AT13387可抑制肿瘤细胞的生长和迁移，并与放射疗法联合使用时具有协同抗癌作用[2]。AT13387常用于非小细胞肺癌（NSCLC）的研究[3]。
AT13387（0.1 - 2.5µM，72小时）以剂量依赖的方式抑制胶质母细胞瘤细胞系的增殖（IC50 ≤ 0.25µM)。AT13387（0.4µM，24小时）可显著抑制胶质瘤细胞的增殖和血管生成能力[4]。
AT13387（5、10mg/kg/天，3天，腹腔注射）显著降低了放射敏感型HCT116人腺癌异种移植小鼠模型的肿瘤生长，并延长了中位生存期和总生存期[2]。
| Cell experiment [1]: | |
Cell lines | LN229, U251HF and A172 Glioblastoma cell lines |
Preparation Method | LN229, U251HF and A172 cells were seeded into 96 well plates and exposed to vehicle control (DMSO) or increasing concentrations of AT13387 (0.1 - 2.5μM) for 72h. Cell viability was measured using the WST-1 assay as per manufacturer’s instructions. |
Reaction Conditions | 0.1 - 2.5µM, 72h |
Applications | AT13387 inhibited cell proliferation in a dose-dependent manner, with an IC50 ≤ 0.25μM. |
| Animal experiment [2]: | |
Animal models | Radiosensitive HCT116 human adenocarcinoma xenograft mouse model |
Preparation Method | Female nu/nu Balb/c mice were housed under standard laboratory conditions and fed ad libitum. Tumor xenografts were formed by subcutaneous inoculation of approximately 1×106 HCT116 cells suspended in 100μL serum free cell culture medium in the right posterior leg. After approximately 10 days tumors had established (> 80mm3) and the treatment schedule started. HCT116 xenografted mice were divided into the following treatment groups: (i) control (N = 10), (ii) radiotherapy (N = 10) 3 × 2 Gy, (iii) AT13387 (N = 10) 3 × 10mg/kg AT13387, (iiii) AT13387 and 3 × 10mg/kg combined with 3 × 2 Gy (N = 10), (iv) AT13387 3 × 5mg/kg (N = 10), (v) AT13387 3 × 5mg/kg combined with 3 × 2 Gy (N = 10). Mice were injected intraperitoneally with 100µL AT13387 or (controls and radiation groups) with 100µL 17.5% β-Cyclodextrin on day 1, 2, and 3. Radiotherapy was given 6h after the drug treatment, performed under anesthesia on day 1, 2, and 3. Tumor size was measured every day with a digital caliper and survival analysis was performed after reaching the study endpoint of 1000mm3 tumor size. |
Dosage form | 5, 10mg/kg/day; 3 days; i.p. |
Applications | AT13387 significantly reduced tumor growth and prolonged both median and overall survival in the HCT116 mouse model. |
References: | |
| Cas No. | 912999-49-6 | SDF | |
| 别名 | AT13387,Onalespib | ||
| 化学名 | (2,4-dihydroxy-5-propan-2-ylphenyl)-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone | ||
| Canonical SMILES | CC(C)C1=C(C=C(C(=C1)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C)O)O | ||
| 分子式 | C24H31N3O3 | 分子量 | 409.5 |
| 溶解度 | ≥ 13.25 mg/mL in DMSO, ≥ 47.7 mg/mL in EtOH with ultrasonic | 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 | 2.442 mL | 12.21 mL | 24.42 mL |
| 5 mM | 488.4 μL | 2.442 mL | 4.884 mL |
| 10 mM | 244.2 μL | 1.221 mL | 2.442 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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