HG-10-102-01 是一种高效、选择性、可透过血脑屏障的LRRK2抑制剂，其对于野生型 LRRK2 和LRRK2[G2019S]，IC50值分别为 20.3 和 3.2 nM。HG-10-102-01也能抑制MNK2和MLK1，其IC50值分别为 0.6 和 2.1 μM。HG-10-102-01 可用于帕金森病 (PD) 的研究。
| 生物活性 | HG-10-102-01 is a highly potent, selective, and brain-penetrableLRRK2inhibitor, withIC50values of 20.3 and 3.2 nM against wild-typeLRRK2andLRRK2[G2019S], respectively. HG-10-102-01 also inhibitsMNK2andMLK1, withIC50values of 0.6 and 2.1 μM. HG-10-102-01 can be used for Parkinson's disease (PD) research[1][2]. |
| IC50& Target | IC50: 3.2 nM (LRRK2[G2019S]), 20.3 nM (wild-type LRRK2), 95.9 nM (LRRK2[G2019S+A2016T], 153.7 nM (LRRK2[A2016T]), 0.6 μM (MNK2), 2.1 μM (MLK1)[1] |
体外研究
(In Vitro) | HG-10-102-01 (0-3 μM, 90 min) substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant[1].
Western Blot Analysis[1] | Cell Line: | HEK293 cells, Mouse Swiss 3T3 cells and Mouse embryonic fibroblast cells | | Concentration: | 0, 0.01, 0.03, 0.1, 0.3, 1, and 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. Induced similar dose-dependent Ser910 and Ser935 dephosphorylation of endogenous LRRK2 in mouse Swiss 3T3 cells and mouse embryonic fibroblast cells. |
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体内研究
(In Vivo) | HG-10-102-01 (0-100 mg/kg, IP, once) shows inhibition of LRRK2 Ser910/Ser935 phosphorylation in kidney, spleen, and brain of mice[1].
HG-10-102-01 (1 mg/kg, IV; 10 mg/kg, PO; once) shows good oral bioavailability (%F = 67), a short half-life of 0.13 h, and low plasma exposure[1].
| Animal Model: | Wild type male C57BL/6 mice[1] | | Dosage: | 0, 3, 10, 30, 50, and 100 mg/kg | | Administration: | IP, once | | Result: | Showed near complete dephosphorylation of Ser910 and Ser935 of LRRK2 in all tissues including brain at 100 mg/kg and 50 mg/kg, but only partial inhibition in brain at the 30 and 10 mg/kg doses. |
| Animal Model: | Wild type male C57BL/6 mice[1] | | Dosage: | 1 mg/kg (IV); 10 mg/kg (PO) | | Administration: | IV, PO; once (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic Parameters of HG-10-102-01 in male C57BL/6 mice[1].
| IV (1 mg/kg) | PO (10 mg/kg) | | Tmax(h) | | 0.25 | | Cmax(ng/mL) | 1330 | 1241 | | AUClast(ng/mL*h) | 74.85 | 502.34 | | AUCINF(ng/mL*h) | 75.06 | 503.41 | | T1/2(h) | 0.13 | | | CL (mL/min/kg) | 222.04 | | | Vss (L/kg) | 1.68 | | | F (%) | | 67 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(132.33 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.6467 mL | 13.2335 mL | 26.4669 mL | | 5 mM | 0.5293 mL | 2.6467 mL | 5.2934 mL | | 10 mM | 0.2647 mL | 1.3233 mL | 2.6467 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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 mg/mL (5.29 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (5.29 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2 mg/mL (5.29 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (5.29 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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