KPT-6566|cas:881487-77-0|西域试剂

KPT-6566,98.0%

产品编号：Bellancom-123847| CAS NO：881487-77-0| 分子式：C₂₂H₂₁NO₅S₂| 分子量：443.54

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货号	价格	库存与货期
Bellancom-123847	￥1200.00	杭州北京（现货）
Bellancom-123847	￥3600.00	杭州北京（现货）
Bellancom-123847	￥5500.00	杭州北京（现货）
Bellancom-123847	￥11000.00	杭州北京（现货）

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KPT-6566

产品介绍

KPT-6566 是一种选择性的、共价的 prolyl 异构酶 PIN1 的抑制剂，共价结合到 PIN1 的催化位点，选择性地抑制和降解 PIN1。KPT-6566 对 PIN1 PPIase domain 的 IC₅₀ 值为 640 nM，K_i 值为 625.2 nM。KPT-6566 可用于癌症的研究。

生物活性

KPT-6566 is a selective and covalent prolyl isomerase PIN1 inhibitor, covalently binds to the catalytic site of PIN1, selectively inhibits and degrades PIN1. KPT-6566 shows an IC₅₀ value of 640 nM and a K_i value of 625.2 nM for PIN1 PPIase domain. KPT-6566 can be used for the research of cancer.

体外研究

KPT-6566 (1-5 μM; 0-8 d) inhibits WT fibroblasts proliferation.
KPT-6566 (0-10 μM; 48 h) inhibits normal breast epithelial cells and cancer cells viability via a PIN1-dependent manner.
KPT-6566 (0-10 μM; 48 h) affects hyperphosphorylated pRB level, Cyclin D1 and PIN1 concentration.
KPT-6566 (2.5-5 μM; 48 h) inhibits the mut-p53, NOTCH1 and NRF2 pathways.
KPT-6566 (0-5 μM; 48 h) induces DNA damage via a PIN1-dependent way.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

Cell Line:	Immortalized fibroblasts derived from WT and Pin1 KO mouse embryos
Concentration:	1 and 5 μM
Incubation Time:	0-8 days
Result:	Dose-dependently inhibited proliferation of WT fibroblasts, while showed no effect on Pin1 KO fibroblasts.

Cell Viability Assay

Cell Line:	MCF10A, HMEC, HeLa, LNCaP, SKOV-3, PANC-1, PC-3, MDA-MB-468 and MDA-MB-231 cells
Concentration:	0-10 μM
Incubation Time:	48 hours
Result:	Inhibited normal breast epithelial cells and cancer cells viability even at a low concentration and increased the concentration of PIN1 in MDA-MB-468, SKOV-3, PC-3, LNCaP and PANC-1.

Western Blot Analysis

Cell Line:	Immortalized fibroblasts derived from WT and Pin1 KO mouse embryos and PIN1 KO MDA-MB-231 cells
Concentration:	0-10 μM
Incubation Time:	48 hours
Result:	Decreased hyperphosphorylated pRB and Cyclin D1 levels, dose- and time-dependently promoted degradation of PIN1 .

Western Blot Analysis

Cell Line:	MDA-MB-231, MCF10A, MDA-MB-468 and MDA-MB-231 cells
Concentration:	0, 2.5 and 5 μM
Incubation Time:	48 hours
Result:	Dose-dependently increased H2AX phosphorylation and caused H2AX phosphorylation in MCF10A, MDA-MB-468 and MDA-MB-231 cell lines. Increased H2AX phosphorylation while other inhibitors such as ATRA, PiB and Juglone disabled to induce H2AX phosphorylation at same concentration. Achieved DNA damage through formation of DNA adducts.

RT-PCR

Cell Line:	MDA-MB-231 cells
Concentration:	2.5 and 5 μM
Incubation Time:	48 hours
Result:	Dose-dependently inhibitd the activation of mut-p53 and NOTCH1 pathways which are controlled by PIN1. Inhibitd the expression of cFOS HO1, NQO1, TXNRD1 and DNAJAB, and induced cellular responses to oxidative stress.

体内研究
(In Vivo)

KPT-6566 (5 mg/kg; i.p. once a day for 26 days) shows no toxicity to mice.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-week-old female mice with 1 million of MDA-MB-231Luc⁶ cells injection
Dosage:	5 mg/kg
Administration:	Intraperitoneal injection; 5 mg/kg once a day; for 26 days
Result:	Exibited no sign of local or systemic and organ toxicity by post mortem morphologic analyses.

体内研究

KPT-6566 (5 mg/kg; i.p. once a day for 26 days) shows no toxicity to mice.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-week-old female mice with 1 million of MDA-MB-231Luc⁶ cells injection
Dosage:	5 mg/kg
Administration:	Intraperitoneal injection; 5 mg/kg once a day; for 26 days
Result:	Exibited no sign of local or systemic and organ toxicity by post mortem morphologic analyses.

体内研究

KPT-6566 (5 mg/kg; i.p. once a day for 26 days) shows no toxicity to mice.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-week-old female mice with 1 million of MDA-MB-231Luc⁶ cells injection
Dosage:	5 mg/kg
Administration:	Intraperitoneal injection; 5 mg/kg once a day; for 26 days
Result:	Exibited no sign of local or systemic and organ toxicity by post mortem morphologic analyses.

性状

Solid

溶解性数据

In Vitro:

DMSO : 19.23 mg/mL (43.36 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	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

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, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: 1.92 mg/mL (4.33 mM); Suspended solution; Need ultrasonic

此方案可获得 1.92 mg/mL (4.33 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 19.2 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 1 mg/mL (2.25 mM); Clear solution

此方案可获得 ≥ 1 mg/mL (2.25 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明