JH-II-127

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

野生型和 G2019S 突变体 LRRK2 的有效选择性抑制剂，IC50 分别为 6.6 和 2.2 nM。

A potent and selective inhibitor of both wild-type and G2019S mutant LRRK2 with IC50 of 6.6 and 2.2 nM, respectively; also inhibits LRRK2 A2016T with IC50 of 47.7 nM; substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at 0.1-0.3 uM in a variety of cell types; inhibits Ser935 phosphorylation in mouse brain; orally active.Parkinson's Disease Preclinical.

JH-II-127 (0.03, 0.1, 0.3, 1, 3 μM; 90 min) inhibits LRRK2 in HEK293 cells.JH-II-127 (0.3, 1, 3 μM; 90 min) inhibits endogenously expressed LRRK2 in mouse Swiss 3T3 cells.Western Blot Analysis Cell Line:HEK293 cells (expressing GFP-LRRK2, GFP-LRRK2[G2019S], GFP-LRRK2[G2019S + A2016T], and GFP-LRRK2[A2016T], respectively )Concentration:0.03, 0.1, 0.3, 1, 3 μMIncubation 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.Inhibited phosphorylation of Ser910 and Ser935 at approximately 0.3 μM for wild-type LRRK2 and LRRK2[G2019S].Induced dephosphorylation of Ser910 and Ser935 at a concentration of 0.3-1 μM in the drug-resistant LRRK2[A2016T + G2019S] and LRRK2[A2016T] mutants.Western Blot Analysis Cell Line:Mouse Swiss 3T3 cellsConcentration:0.03, 0.1, 0.3, 1, 3 μM Incubation Time:90 min Result:Induced similar dose-dependent Ser935 dephosphorylation of endogenous LRRK2.

JH-II-127 (100 mg/kg; i.p.; single) results in near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain.Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice.Animal Model:Wild type male C57BL/6 mice.Dosage:2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.)Administration:Intravenous and intraperitoneal injection; oral administration; single.Result:Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose.

JH-II-127 | JH-II 127 | JH-II127

Autophagy

LRRK2

LRRK2

Neurological Disease

Parkinson Disease

1700693-08-8

416.8615

C19H21ClN6O3

>98% (HPLC)

DMSO: ≥ 30 mg/mL

ClC1=CNC2=C1C(NC)=NC(NC3=C(OC)C=C(C(N4CCOCC4)=O)C=C3)=N2

Methanone, [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinyl-

(-20℃)

With Ice Pack

≥ 2 years