JH-II-127

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^[1]. In Vitro:JH-II-127 (0.03, 0.1, 0.3, 1, 3 µM; 90 min) inhibits LRRK2 in HEK293 cells^[1].
JH-II-127 (0.3, 1, 3 µM; 90 min) inhibits endogenously expressed LRRK2 in mouse Swiss 3T3 cells^[1]. 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].
Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice^[1].

matrix	route	Tmax (h)	C0/Cmax (ng/mL)	AUCLast (h•ng/mL)	AUGINF (h•ng/mL)	T1/2 (h)	CL (mL/min/kg)	Vss (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	-	-	-