JH-II-127|cas:1700693-08-8|西域试剂

JH-II-127,98.02%

产品编号：Bellancom-16936| CAS NO：1700693-08-8| 分子式：C₁₉H₂₁ClN₆O₃| 分子量：416.86

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货号	价格	库存与货期
Bellancom-16936	￥933.00	杭州北京（现货）
Bellancom-16936	￥1400.00	杭州北京（现货）
Bellancom-16936	￥2200.00	杭州北京（现货）
Bellancom-16936	￥6600.00	杭州北京（现货）
Bellancom-16936	￥11000.00	杭州北京（现货）

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JH-II-127

产品介绍

JH-II-127一种口服有效的，具有高效力、选择性和脑渗透性的 LRRK2 抑制剂，其对野生型的 LRRK2 和LRRK2-G2019S 以及突变型的 LRRK2-A2016T 的 IC₅₀ 值分别为6、2 和 48 nM。JH-II-127 能够抑制小鼠包括大脑在内的所有组织中的 Ser935 磷酸化。JH-II-127 可用于帕金森综合征的研究。

生物活性

JH-II-127 is an orally active, highly potent, selective and brain-permeable LRRK2 inhibitor, with IC₅₀s of 6, 2 and 48 nM for wild-type LRRK2 and LRRK2-G2019S and mutant LRRK2-A2016T. JH-II-127 inhibits Ser935 phosphorylation in all tissues of mice, including the brain. JH-II-127 can be used in the study of parkinson's syndrome.

体外研究

JH-II-127 (0.03, 0.1, 0.3, 1, 3 µM; 90 min) inhibits LRRK2 in HEK293 cells.
JH-II-127 (0.3, 1, 3 µM; 90 min) inhibits endogenously expressed LRRK2 in mouse Swiss 3T3 cells.

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

Western Blot Analysis

Cell Line:	HEK293 cells (expressing GFP-LRRK2, GFP-LRRK2[G2019S], GFP-LRRK2[G2019S + A2016T], and GFP-LRRK2[A2016T], respectively)
Concentration:	0.03, 0.1, 0.3, 1, 3 µM
Incubation Time:	90 min
Result:	Induced a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells. Inhibited phosphorylation of Ser910 and Ser935 at approximately 0.3 μM for wild-type LRRK2 and LRRK2[G2019S]. Induced dephosphorylation of Ser910 and Ser935 at a concentration of 0.3-1 μM in the drug-resistant LRRK2[A2016T + G2019S] and LRRK2[A2016T] mutants.

Western Blot Analysis

Cell Line:	Mouse Swiss 3T3 cells
Concentration:	0.03, 0.1, 0.3, 1, 3 µM
Incubation Time:	90 min
Result:	Induced similar dose-dependent Ser935 dephosphorylation of endogenous LRRK2.

体内研究
(In Vivo)

JH-II-127 (100 mg/kg; i.p.; single) results in near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain.
1.19 Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice.

matrix	route	T_max (h)	C₀/C_max (ng/mL)	AUC_Last (h•ng/mL)	AUG_INF (h•ng/mL)	T_1/2 (h)	CL (mL/min/kg)	V_ss (L/kg)
plasma	IV (2 mg/kg)	-	1604.47	532.67	535.57	0.66	62.24	1.73
plasma	PO (10 mg/kg)	1	802.72	3094.58	3867.07	-	-	-
brain	IV (2 mg/kg)	-	1343.6	239.31	246.47	0.23	135.24	1.7
brain	PO (10 mg/kg)	1	247.35	688.21	762.38	-	-	-

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

Animal Model:	Wild type male C57BL/6 mice.
Dosage:	2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.)
Administration:	Intravenous and intraperitoneal injection; oral administration; single.
Result:	Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose. Demonstrated good oral bioavailability.

体内研究

matrix	route	T_max (h)	C₀/C_max (ng/mL)	AUC_Last (h•ng/mL)	AUG_INF (h•ng/mL)	T_1/2 (h)	CL (mL/min/kg)	V_ss (L/kg)
plasma	IV (2 mg/kg)	-	1604.47	532.67	535.57	0.66	62.24	1.73
plasma	PO (10 mg/kg)	1	802.72	3094.58	3867.07	-	-	-
brain	IV (2 mg/kg)	-	1343.6	239.31	246.47	0.23	135.24	1.7
brain	PO (10 mg/kg)	1	247.35	688.21	762.38	-	-	-

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

Animal Model:	Wild type male C57BL/6 mice.
Dosage:	2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.)
Administration:	Intravenous and intraperitoneal injection; oral administration; single.
Result:	Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose. Demonstrated good oral bioavailability.

体内研究

matrix	route	T_max (h)	C₀/C_max (ng/mL)	AUC_Last (h•ng/mL)	AUG_INF (h•ng/mL)	T_1/2 (h)	CL (mL/min/kg)	V_ss (L/kg)
plasma	IV (2 mg/kg)	-	1604.47	532.67	535.57	0.66	62.24	1.73
plasma	PO (10 mg/kg)	1	802.72	3094.58	3867.07	-	-	-
brain	IV (2 mg/kg)	-	1343.6	239.31	246.47	0.23	135.24	1.7
brain	PO (10 mg/kg)	1	247.35	688.21	762.38	-	-	-

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

Animal Model:	Wild type male C57BL/6 mice.
Dosage:	2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.)
Administration:	Intravenous and intraperitoneal injection; oral administration; single.
Result:	Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose. Demonstrated good oral bioavailability.

性状

Solid

溶解性数据

In Vitro:

DMSO : 110 mg/mL (263.88 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3989 mL	11.9944 mL	23.9889 mL
5 mM	0.4798 mL	2.3989 mL	4.7978 mL
10 mM	0.2399 mL	1.1994 mL	2.3989 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 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.75 mg/mL (6.60 mM); Clear solution

此方案可获得 ≥ 2.75 mg/mL (6.60 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 27.5 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% corn oil
Solubility: ≥ 2.75 mg/mL (6.60 mM); Clear solution

此方案可获得 ≥ 2.75 mg/mL (6.60 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 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。