KPT-6566 |
| Katalog-Nr.GC38577 |
KPT-6566 ist ein selektiver und kovalenter Prolylisomerase-PIN1-Inhibitor, der kovalent an die katalytische Stelle von PIN1 bindet, PIN1 selektiv hemmt und abbaut. KPT-6566 zeigt einen IC50-Wert von 640nM und einen Ki-Wert von 625,2 nM fÜr die PIN1-PPIase-DomÄne. KPT-6566 kann fÜr die Krebsforschung eingesetzt werden.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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. |
|
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 | |
| 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 | ||
| Formula | C22H21NO5S2 | M.Wt | 443.54 |
| Löslichkeit | DMSO : 19.23 mg/mL (43.36 mM; Need ultrasonic) | Storage | 4°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)
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