| Hazard Information | Back Directory | [Uses]
XL01126 is a potent LRRK2 PROTAC (DC50: 14 nM (G2019S LRRK2) and 32 nM (WT LRRK2)) composed of the VHL ligand VH 101, thiol (HY-47851, blue part) and the LRRK2 inhibitor HG-10-102-01 (HY-13488, red part). XL01126 crosses the blood-brain barrier and is used as a degradation probe in Parkinson's disease research. XL01126 can be used to study the non-catalytic and framework functions of LRRK2[1]. | [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 |
| [References]
[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. DOI:10.1021/jacs.2c05499 |
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