2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
生物活性
Description
In Vivo
In Vitro
化合物的使用
Kinase Assay
Cell Assay
Animal Administration
参考文献
HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)
HG-10-102-01 maintains the ability to potently inhibit the biochemical activity of wild-type and G2019S mutant LRRK2. HG-10-102-01 exhibited biochemical IC50s of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. At a concentration of 10 ?M, HG-10-102-01 only inhibited the kinase activities of MLK1 and MNK2 to greater than 80% of the DMSO control. Dose-response analysis revealed inhibition of MLK1 with an IC50 2.1 ?M and MNK2 with an IC50 0.6 ?M. KinomeScan analysis against a near comprehensive panel of 451 kinases at a concentration of 1 ?M resulted in no interactions detected with kinases other than G2019S LRRK2 with the exception of one mutant form of c-Kit (L576P) demonstrating the outstanding selectivity of this inhibitor.
HG-10-102-01 significantly inhibited phosphorylation of wildtype LRRK2 and LRRK2[G2019S] mutant at Ser910 and Ser935 at 0.3-1.0 ?M in cell culture, which is approximately the same potency as LRRK2-IN-1 (1). HG-10-102-01 is relatively insensitive to the A2016T mutation which suggests that this mutant will not be useful to validate whether the pharmacological effects of the compound are LRRK2-dependent.
HG-10-102-01 can inhibit phosphorylation of Ser910 and Ser935 of LRRK2 in brain and peripheral tissues following intraperitoneal doses of 50 mg/kg. Further optimization of this chemo-type especially in regards to in vivo half-life will be reported in due course.
