XL01126 是一种强效的LRRK2降解剂，DC50分别为 14 nM (G2019S LRRK2) 和 32 nM (WT LRRK2)。XL01126 可透过血脑屏障，并作为降解探针，用于帕金森疾病的研究。XL01126 能在LRRK2的非催化和框架功能的研究中发挥作用。
| 生物活性 | XL01126 is a potent degrader ofLRRK2withDC50s of 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2), respectively. XL01126 can cross blood-brain barrier and be used as a degrader probe in Parkinson’s disease research. XL01126 exerts function of study of non-catalytic and scaffolding functions ofLRRK2[1]. |
| IC50& Target | DC50: 15-72 nM (LRRK2)[1] |
体外研究
(In Vitro) | XL01126 (300 nM; 4 h) exhibits strong degradation performance by forming a positively cooperative ternary complex with E3 ubiquitin ligase ligand VHL and target protein LRRK2[1].
XL01126 (10, 30, 100 nM; 24 h) increases mitophagy in immortalized mouse embryonic fibroblasts cells[1].
XL01126 (10 μM; 90 min) displays high permeability in Caco-2 cells[1].
XL01126 (10 μM; 0-60 min; every 15 min interval gradient) exhibits high stability in mouse plasma, liver microsome and hepatocyte[1].
Pharmacokinetic of XL01126 in vitro[1]
| Parameter | Properties | | T1/2in mouse plasma | 108.29 min | | T1/2in mouse liver microsome | 3.65 min | | Clintin mouse liver microsome | 1494.62 mL/min/kg | | T1/2in mose hepatocytes | 314.33 min | | Clintin mose hepatocytes | 26.04 mL/min/kg |
Western Blot Analysis[1] | Cell Line: | G2019S LRRK2 MEFs (mouse embryonic fibroblasts) | | Concentration: | 300 nM | | Incubation Time: | 4 hours | | Result: | Resulted LRRK2 pSer935, Rab10 pThr73 decrease. |
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体内研究
(In Vivo) | XL01126 (30 mg/kg; p.o.; single dose) shows oral activity with bioavailable value (F) of 15% and can penetrate the blood brain barrier after either oral or parenteral dosing in mice[1].
Pharmacokinetic property of XL01126 in mice[1]
| Route | Dose
(mg/kg) | CL
(L/h/kg) | Vss
(L/kg) | Tmax
(h) | Cmax
(ng/mL) | T1/2
(h) | AUClast
(h·ng/mL) | AUCinf
(h·ng/mL) | MRT
(h) | F
(%) | | p.o. | 30 | | | 2 | 3620 | 21.9 | 21337 | 109271 | | 15 | | i.v. | 5 | 0.208 | 0.511 | | | 1.52 | 23663 | 23981 | 2.45 | | | i.p. | 30 | | | 0.25 | 7700 | 5.2 | 41434 | 64068 | | 29.2 |
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| 分子量 | |
| 性状 | |
| Formula | |
| 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 : ≥ 100 mg/mL(98.07 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 0.9807 mL | 4.9035 mL | 9.8069 mL | | 5 mM | 0.1961 mL | 0.9807 mL | 1.9614 mL | | 10 mM | 0.0981 mL | 0.4903 mL | 0.9807 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。 |
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