J22352
目录号 : GC34629
J22352是一种具有类似靶向嵌合体蛋白水解(PROTAC)特性、高度选择性HDAC6抑制剂，其IC50值为4.7nM，J22352通过抑制胶质母细胞瘤自噬、诱发抗肿瘤免疫反应来促进HDAC6降解和诱导抗癌效果，并通过降低PD-L1的免疫抑制活性，使宿主抗肿瘤活性恢复。
Cas No.:2252395-44-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
J22352 is a PROTAC (proteolysis-targeting chimeras)-like and highly selective HDAC6 inhibitor with an IC50 value of 4.7 nM. J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma cancers, and leading to the restoration of host antitumor activity by reducing the immunosuppressive activity of PD-L1[1]. HDAC6|4.7 nM (IC50)
J22352 (0.1-20 μM; 72 hours) decreases U87MG cell viability in a dose-dependent manner[1]. J22352 (10 μM; 24 hours) shows a dose-dependent decrease in HDAC6 protein abundance[1]. Cell Viability Assay[1] Cell Line: U87MG cells
J22352 (10mg/kg; given i.p. per day for 14 days in male nude mice) results in a >80% tumor growth inhibition (TGI) rate. J22352 is well tolerated in mice[1]. Animal Model: Male nude mice (BALB/cAnN.Cg-Foxnlnu/CrlNarl, 4-6 weeks old)[1]
[1]. Liu JR, et al. High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma. Biochem Pharmacol. 2019 May; 163:458-471.
| Cas No. | 2252395-44-9 | SDF | |
| Canonical SMILES | O=C(C1=CC=CC=C1N2CC3=CC=C(C(NO)=O)C=C3)N(CCC4=CC=CC=C4)C2=O | ||
| 分子式 | C24H21N3O4 | 分子量 | 415.44 |
| 溶解度 | DMSO: 125 mg/mL (300.89 mM) | 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 | 2.4071 mL | 12.0354 mL | 24.0709 mL |
| 5 mM | 0.4814 mL | 2.4071 mL | 4.8142 mL |
| 10 mM | 0.2407 mL | 1.2035 mL | 2.4071 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。
High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma
Biochem Pharmacol 2019 May;163:458-471.PMID:30885763DOI:10.1016/j.bcp.2019.03.023
Glioblastoma is the most fatal type of primary brain cancer, and current treatments for glioblastoma are insufficient. HDAC6 is overexpressed in glioblastoma, and siRNA-mediated knockdown of HDAC6 inhibits glioma cell proliferation. Herein, we report a high-selective HDAC6 inhibitor, J22352, which has PROTAC (proteolysis-targeting chimeras)-like property resulted in both p62 accumulation and proteasomal degradation, leading to proteolysis of aberrantly overexpressed HDAC6 in glioblastoma. The consequences of decreased HDAC6 expression in response to J22352 decreased cell migration, increased autophagic cancer cell death and significant tumor growth inhibition. Notably, J22352 reduced the immunosuppressive activity of PD-L1, leading to the restoration of host anti-tumor activity. These results demonstrate that J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma. Therefore, this highly selective HDAC6 inhibitor can be considered a potential therapeutic for the treatment of glioblastoma and other cancers.