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KPT-6566
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
KPT-6566图片
规格:98%
分子量:443.54

KPT-6566 是一种有效、选择性、共价结合的脯氨酰异构酶 PIN1 抑制剂,与 PIN1 的催化位点共价结合,抑制并降解 PIN1。KPT-6566 对 PIN1 PPIase 结构域的 IC50 和 Ki 值分别为 640 nM 和 625.2 nM。KPT-6566 具有抗癌作用。
货号:ajcx14998
CAS:881487-77-0
分子式:C22H21NO5S2
分子量:443.54
溶解度:DMSO : 19.23 mg/mL?(43.36 mM;?Need ultrasonic)
纯度:98%
存储:Store at -20°C
库存:现货

Background:

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-1i.p) or the vehicle, after 27 days found that the metastatic growth in KPT-6566 treated animals was significantly reduced compared to controls.[2]

参考文献:
[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.

Protocol:

Cell experiment [1]:

Cell lines

MEF cells

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]:

Animal models

Nude mice

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.

参考文献:

[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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