PK68|cas:2173556-69-7|西域试剂

PK68,99.92%

产品编号：Bellancom-128348| CAS NO：2173556-69-7| 分子式：C₂₂H₂₄N₄O₃S| 分子量：424.52

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-128348	￥3500.00	杭州北京（现货）
Bellancom-128348	￥6500.00	杭州北京（现货）
Bellancom-128348	￥19500.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

PK68

产品介绍

PK68 是一种高效、特异性的受体相互作用激酶 1 (RIPK1) 的 II 型抑制剂，具有口服活性。其 IC₅₀ 值约 90 nM，可抑制 RIPK1 依赖性坏死。PK68 对 TNF 诱导的全身炎症反应综合征有较强的改善作用，可用于炎症紊乱和肿瘤转移的研究。

生物活性

PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC₅₀ of ~90 nM, displays inhibition of RIPK1-dependent necroptosis. PK68 powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and can be used for the research of inflammatory disorders and cancer metastasis.

体外研究

PK68 has highly potent inhibition of TNF-induced necroptosis with EC₅₀ values of 23 nM and 13 nM in human and mouse cells, respectively.
PK68 is a highly selective inhibitor of RIPK1 kinase activity with IC₅₀ value of 90 nM.
PK68 (100 nM, 1 h) blocks necroptosis through the suppression of RIPK3 function or signaling upstream of RIPK3 activation.

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

Cell Viability Assay

Cell Line:	Bone marrow-derived macrophages, NIH3T3-RIPK3 cells
Concentration:	100 nM
Incubation Time:	1 h
Result:	PK68 block cellular activation of RIPK1, RIPK3, and MLKL upon necroptotic stimuli. PK68 inhibit TNF-induced necroptosis but not RIPK3 dimerization-induced cell death in NIH3T3-RIPK3 cells.

Western Blot Analysis

Cell Line:	HT-29 cells
Concentration:	100 nM
Incubation Time:	1 h
Result:	Completely abolished phosphorylation of RIPK1, RIPK3, and MLKL.

Immunofluorescence

Cell Line:	HT-29 cells
Concentration:	100 nM
Incubation Time:	1 h
Result:	Prevented generation of RIPK3 puncta.

体内研究
(In Vivo)

PK68 (5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days) or (2 mg/kg, i.v.; 10 mg/kg, p.o.; for 14 days) exhibits a favorable pharmacokinetic profile and no obvious toxicity in mice.
PK68 (1 mg/kg, i.p.) ameliorates TNF-induced systemic inflammatory response syndrome.
PK68 (5 mg/kg, i.v.) inhibits RIPK1 that results in attenuated tumor cell transmigration across the endothelial barrier and preventive suppression of tumor metastasis.

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

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg, 25 mg/kg
Administration:	5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days
Result:	Exhibited favorable pharmacokinetic profiles and no obvious toxicity in mice treated with a 14-day course at a dose of 25 mg/kg.

Animal Model:

C57BL/6 mice

Dosage:

2 mg/kg, 10 mg/kg

Administration:

2 mg/kg, i.v.; 10 mg/kg, p.o; for 14 days

Result:

	PO (Gavage)	IV (Bolus)
T_max (hr)	0.5
C_max (ng/mL)	2423
AUC_0-24 (ng/mL•hr)	4821	1588
AUCINF (ng/mL•hr)	4897	1590
t_1/2 (hr)	1.3	1.0
MRT (hr)	1.8	0.8
CL (mL/hr/kg)		1258
CL (mL/min/kg)		21
Vss (mL/kg)		1009
Vss (L/kg)		1.0
F(%)	61

Animal Model:	C57BL/6 mice
Dosage:	1 mg/kg
Administration:	1 mg/kg, i.p.
Result:	Provided effective protection against TNFα-induced lethal shock.

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg
Administration:	5 mg/kg, i.v.
Result:	Significantly reduced the number of pulmonary metastasis nodules, decreased lung metastasis, decreased number of RFP-LL/2 cells, attenuated transmigration of RFP-LL/2 cells through the endothelial cell monolayer and had no obvious influence on the proliferation rate and invasion ability of B16-F10 or RFP-LL/2 cells without the endothelial cell monolayer in vitro.

体内研究

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

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg, 25 mg/kg
Administration:	5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days
Result:	Exhibited favorable pharmacokinetic profiles and no obvious toxicity in mice treated with a 14-day course at a dose of 25 mg/kg.

Animal Model:

C57BL/6 mice

Dosage:

2 mg/kg, 10 mg/kg

Administration:

2 mg/kg, i.v.; 10 mg/kg, p.o; for 14 days

Result:

	PO (Gavage)	IV (Bolus)
T_max (hr)	0.5
C_max (ng/mL)	2423
AUC_0-24 (ng/mL•hr)	4821	1588
AUCINF (ng/mL•hr)	4897	1590
t_1/2 (hr)	1.3	1.0
MRT (hr)	1.8	0.8
CL (mL/hr/kg)		1258
CL (mL/min/kg)		21
Vss (mL/kg)		1009
Vss (L/kg)		1.0
F(%)	61

Animal Model:	C57BL/6 mice
Dosage:	1 mg/kg
Administration:	1 mg/kg, i.p.
Result:	Provided effective protection against TNFα-induced lethal shock.

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg
Administration:	5 mg/kg, i.v.
Result:	Significantly reduced the number of pulmonary metastasis nodules, decreased lung metastasis, decreased number of RFP-LL/2 cells, attenuated transmigration of RFP-LL/2 cells through the endothelial cell monolayer and had no obvious influence on the proliferation rate and invasion ability of B16-F10 or RFP-LL/2 cells without the endothelial cell monolayer in vitro.

体内研究

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

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg, 25 mg/kg
Administration:	5 mg/kg, 25 mg/kg; oral gavage; daily; for 7 days
Result:	Exhibited favorable pharmacokinetic profiles and no obvious toxicity in mice treated with a 14-day course at a dose of 25 mg/kg.

Animal Model:

C57BL/6 mice

Dosage:

2 mg/kg, 10 mg/kg

Administration:

2 mg/kg, i.v.; 10 mg/kg, p.o; for 14 days

Result:

	PO (Gavage)	IV (Bolus)
T_max (hr)	0.5
C_max (ng/mL)	2423
AUC_0-24 (ng/mL•hr)	4821	1588
AUCINF (ng/mL•hr)	4897	1590
t_1/2 (hr)	1.3	1.0
MRT (hr)	1.8	0.8
CL (mL/hr/kg)		1258
CL (mL/min/kg)		21
Vss (mL/kg)		1009
Vss (L/kg)		1.0
F(%)	61

Animal Model:	C57BL/6 mice
Dosage:	1 mg/kg
Administration:	1 mg/kg, i.p.
Result:	Provided effective protection against TNFα-induced lethal shock.

Animal Model:	C57BL/6 mice
Dosage:	5 mg/kg
Administration:	5 mg/kg, i.v.
Result:	Significantly reduced the number of pulmonary metastasis nodules, decreased lung metastasis, decreased number of RFP-LL/2 cells, attenuated transmigration of RFP-LL/2 cells through the endothelial cell monolayer and had no obvious influence on the proliferation rate and invasion ability of B16-F10 or RFP-LL/2 cells without the endothelial cell monolayer in vitro.

性状

Solid

溶解性数据

In Vitro:

DMSO : 30 mg/mL (70.67 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3556 mL	11.7780 mL	23.5560 mL
5 mM	0.4711 mL	2.3556 mL	4.7112 mL
10 mM	0.2356 mL	1.1778 mL	2.3556 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。-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 90% (20% SBE-β-CD in saline)
Solubility: ≥ 3 mg/mL (7.07 mM); Clear solution

此方案可获得 ≥ 3 mg/mL (7.07 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 30.0 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
2.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (4.90 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.90 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.90 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.90 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。