| Bioactivity | XL01126 is a potent degrader of LRRK2 with DC50s 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 of LRRK2[1]. | ||||||||||||
| Target | DC50: 15-72 nM (LRRK2) | ||||||||||||
| Invitro | 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 | ||||||||||||
| 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 | ||||||||||||
| Name | XL01126 | ||||||||||||
| Formula | C50H64ClFN10O6S2 | ||||||||||||
| Molar Mass | 1019.69 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Liu, Xingui, et al. Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bi- oavailable and Blood Brain Barrier Penetrant PROTAC Degrader of Leucine Rich Repeat Kinase 2 (LRRK2). 2022. |