HG-10-102-01

Research use only, not for human use.

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2 IC50 of 20.3 nM).

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2 IC50 of 20.3 nM).

HG-10-102-01 (0-3 μM, 90 min) substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant.Western Blot AnalysisCell 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.

HG-10-102-01 (0-100 mg/kg, IP, once) shows inhibition of LRRK2 Ser910/Ser935 phosphorylation in kidney, spleen, and brain of mice.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. Animal Model:Wild type male C57BL/6 mice 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 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.

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Autophagy

LRRK2

LRRK2

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1351758-81-0

377.83

C17H20ClN5O3

>98% (HPLC)

DMSO:50 mg/mL (132.33 mM)

CNc1nc(Nc2ccc(cc2OC)C(=O)N2CCOCC2)ncc1Cl

[4-[[5-chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinyl-methanone

(-20℃)

With Ice Pack

≥ 2 years