KPT-6566
(Synonyms: 2-[[4-[[[4-(叔丁基)苯基]磺酰基]亚氨基]-1-氧代-1,4-二氢-2-萘基]硫基]乙酸) 目录号 : GC38577
KPT-6566 是一种新型 Pin1 特异性抑制剂。
Cas No.:881487-77-0
Sample solution is provided at 25 µL, 10mM.
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KPT-6566 is a novel Pin1-specific inhibitor. KPT-6566 covalently can bind to the catalytic site of it and targets Pin1 for degradation. KPT-6566 is also able to specifically inhibit the vitality of Pin1-overexpressing cancer cells while not affecting normal cells.[1] Moreover, the IC50 values of KPT-6566 for HeLa and SiHa cells were 13.5 and 14.3 μM, respectively. Combination KPT-6566 with DDP treatment group was obiviously higher than that observed in the DDP group in terms of the apoptosis rate of HeLa/SiHa cells.[1]
In vitro experiment it shown that treatment with 2, 4, 6 and 8 μM KPT-6566 of cells enhanced the killing effect of HeLa/SiHa cells by DDP. In addition, treatment with 5 μM KPT-6566 of Hela/SiHa cells, the results exhibited a significant decrease in the abundance of Pin1 and its downstream oncoproteins, including c-Jun, cyclin D1, β-catenin, ERK1/2, p-ERK, AKT, and p-AKT473.[1]
KPT-6566 (5 mg/kg) inhibited the migration and invasion of CCCs in vivo. In vivo experiment it demonstrated that the mice carried 60 mm3 tumor were treated with 20 mg/kg DDP, 5 mg/kg KPT-6566, a combination of DDP and KPT-6566, KPT-6566 and DDP alone mildly inhibited the tumour growth in nude mice, whereas the combination of KPT-6566 with DDP significantly inhibited tumour growth.[1] By tail vein injection of MDA-MB-231 cells in nude mice (15 animals), then the day after cancer cell injection, mice were randomized in two groups to be treated daily with either KPT-6566 (5?mg?kg-1 i.p) or the vehicle, after 27 days found that the metastatic growth in KPT-6566 treated animals was significantly reduced compared to controls.[2]
References:
[1].Guo YT, et al. Predictive Value of Pin1 in Cervical Low-Grade Squamous Intraepithelial Lesions and Inhibition of Pin1 Exerts Potent Anticancer Activity against Human Cervical Cancer. Aging Dis. 2020 Feb 1;11(1):44-59.
[2].Campaner E, et al. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action. Nat Commun. 2017 Jun 9;8:15772.
KPT-6566 是一种新型 Pin1 特异性抑制剂。 KPT-6566 可以共价结合到它的催化位点并靶向 Pin1 进行降解。 KPT-6566 还能够特异性抑制 Pin1 过表达癌细胞的活力，而不影响正常细胞。[1] 此外，KPT-6566 对 HeLa 和 SiHa 细胞的 IC50 值为 13.5 和分别为 14.3 μM。 KPT-6566联合DDP处理组对HeLa/SiHa细胞凋亡率明显高于DDP组。[1]
体外实验表明，用2、4、6和8μM KPT-6566处理细胞可增强DDP对HeLa/SiHa细胞的杀伤作用。此外，用 5 μM KPT-6566 处理 Hela/SiHa 细胞，结果显示 Pin1 及其下游癌蛋白的丰度显着降低，包括 c-Jun、细胞周期蛋白 D1、β-catenin、ERK1/2、p- ERK、AKT 和 p-AKT473。[1]
KPT-6566 (5 mg/kg) 在体内抑制 CCC 的迁移和侵袭。体内实验表明，携带 60 mm3 肿瘤的小鼠用 20 mg/kg DDP、5 mg/kg KPT-6566、DDP 和 KPT-6566 的组合、单独的 KPT-6566 和 DDP 轻度抑制肿瘤生长裸鼠，而 KPT-6566 与 DDP 的组合显着抑制肿瘤生长。[1] 通过尾静脉注射 MDA-MB-231 细胞给裸鼠（15 只动物），然后在第二天癌细胞注射后，小鼠被随机分为两组，每天接受 KPT-6566（5 mg kg-1 i.p）或载体治疗，27 天后发现 KPT-6566 中的转移性生长与对照组相比，接受治疗的动物显着减少。[2]
| Cell experiment [1]: | |
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Cell lines |
MEF cells |
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Preparation Method |
Growth curves of WT or Pin1 KO MEFs treated with the indicated concentrations of KPT-6566 (5 μM) or DMSO. Immunoblotting of the indicated cell cycle-related proteins in WT or Pin1 KO MEFs treated with 5 μM KPT-6566 (+) or DMSO (−) for 48 h. |
|
Reaction Conditions |
5 μM, 48h |
|
Applications |
In WT MEFs KPT-6566 had a negative, dose-dependent effect on proliferation and induced a decrease of hyperphosphorylated pRB and Cyclin D1 levels. |
| Animal experiment [2]: | |
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Animal models |
Nude mice |
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Preparation Method |
When the tumour volumes reached 60 mm3, the mice were randomly grouped into four groups and treated with 20 mg/kg DDP, 5 mg/kg KPT-6566, a combination of DDP and KPT-6566 or a saline vehicle. |
|
Dosage form |
5 mg/kg, i.p. |
|
Applications |
KPT-6566 and DDP alone mildly inhibited the tumour growth in nude mice, whereas the combination of KPT-6566 with DDP significantly inhibited tumour growth. |
|
References: [1]. Campaner E, et al. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action. Nat Commun. 2017 Jun 9;8:15772. [2]. Guo YT, et al. Predictive Value of Pin1 in Cervical Low-Grade Squamous Intraepithelial Lesions and Inhibition of Pin1 Exerts Potent Anticancer Activity against Human Cervical Cancer. Aging Dis. 2020 Feb 1;11(1):44-59. |
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| Cas No. | 881487-77-0 | SDF | |
| 别名 | 2-[[4-[[[4-(叔丁基)苯基]磺酰基]亚氨基]-1-氧代-1,4-二氢-2-萘基]硫基]乙酸 | ||
| Canonical SMILES | O=C(O)CSC(C1=O)=C/C(C2=C1C=CC=C2)=N\S(=O)(C3=CC=C(C(C)(C)C)C=C3)=O | ||
| 分子式 | C22H21NO5S2 | 分子量 | 443.54 |
| 溶解度 | DMSO : 19.23 mg/mL (43.36 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light, stored under nitrogen |
| 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 | 2.2546 mL | 11.2729 mL | 22.5459 mL |
| 5 mM | 0.4509 mL | 2.2546 mL | 4.5092 mL |
| 10 mM | 0.2255 mL | 1.1273 mL | 2.2546 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet