LRRK2-IN-1-Calbiochem

半岛bd体育手机客户端 说明

一般描述

A cell-permeable, ATP competitive, potent, and selective LRRK2 inhibitor (IC₅₀of 13 nM, 6 nM, and 2.45 ?M for wild type, G2019S mutant, and drug resistant A2016T mutant LRRK2, respectively, in anin vitroATP-site competititon binding assay). While it is shown to inhibit DCLK2 (IC₅₀= 45 nM) and suppress MAPK7 autophosphorylation (EC₅₀= 160 nM), this compound (<10 ?M) demonstrates very good overall selectivity, targeting 12 out of 442 other kinases in a kinase-binding and biochemical assay. At 0.05-3 ?M, it induces dose-dependent inhibition of Ser⁹¹⁰and Ser⁹³⁵phosphorylation accompanied by loss of 14-3-3 binding to both wild-type LRRK2 and LRRK2[G2019S] in stably transfected HEK293 cells, but not in the drug-resistant LRRK2[A2016T] and LRRK2[A2016T + G2019S] mutants. Similar effects on endogenous LRRK2 phosphorylation and 14-3-3 binding can be observed in human lympho-blastoid cells and for the LRRK2 G2019S mutant derived from a Parkinson′s disease patient, and in human-derived neuroblastoma SHSY5Y cells, as well as in mouse Swiss 3T3 cells. 100 mg/kg of compound injected into mice elicits complete Ser⁹¹⁰and Ser⁹³⁵dephosphorylation of LRRK2 in the kidney, but not in the brain which may result from an inability to penetrate the blood-brain barrier. In addition, it promotes relocalization of LRRK2 to more aggregate and fibrillar-like structures.
A cell-permeable, ATP competitive, potent, and selective LRRK2 inhibitor (IC₅₀of 13 nM, 6 nM, and 2.45 ?M for wild type, G2019S mutant, and drug resistant A2016T mutant LRRK2, respectively, in anin vitroATP-site competititon binding assay). While it is shown to inhibit DCLK2 (IC₅₀= 45 nM) and suppress MAPK7 autophosphorylation (EC₅₀= 160 nM), this compound (<10 ?M) demonstrates very good overall selectivity, targeting 12 out of 442 other kinases in a kinase-binding and biochemical assay. At 0.05–3 ?M, it induces dose-dependent inhibition of Ser910 and Ser935 phosphorylation accompanied by loss of 14-3-3 binding to both wild-type LRRK2 and LRRK2[G2019S] in stably transfected HEK293 cells, but not in the drug-resistant LRRK2[A2016T] and LRRK2[A2016T + G2019S] mutants. Similar effects on endogenous LRRK2 phosphorylation and 14-3-3 binding can be observed in human lympho?blastoid cells and for the LRRK2 G2019S mutant derived from a Parkinson′s disease patient, and in human-derived neuroblastoma SHSY5Y cells, as well as in mouse Swiss 3T3 cells. 100 mg/kg of compound injected into mice elicits complete Ser910 and Ser935 dephosphorylation of LRRK2 in the kidney, but not in the brain which may result from an inability to penetrate the blood-brain barrier. In addition, it promotes relocalization of LRRK2 to more aggregate and fibrillar-like structures.

包装

5 mg in Glass bottle
Packaged under inert gas

警告

Toxicity: Regulatory Review (Z)

重悬

Following reconstitution, aliquot and freexe (-20°C). Stock solutions are stable for up to 3 months at -20°C.

其他说明

Deng, X., et al. 2011.Nat. Chem. Biol.7,203.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

经验(实验)分子式	C31H38N8O3
分子量	570.69

半岛bd体育手机客户端 性质

质量水平	100
测定	≥95% (HPLC)
形式	powder
manufacturer/tradename	Calbiochem?
储存条件	OK to freeze protect from light
颜色	yellow-white to pale yellow
溶解性	DMSO: 50 mg/mL
运输	ambient
储存温度	2-8℃

安全信息

储存分类代码	11 - Combustible Solids
WGK	WGK 3
闪点(F)	Not applicable
闪点(C)	Not applicable