LRRK2-IN-1 - Calbiochem Chemische Eigenschaften,Einsatz,Produktion Methoden
Allgemeine Beschreibung
A cell-permeable, ATP competitive, potent, and selective LRRK2 inhibitor (IC
50 of 13 nM, 6 nM, and 2.45 μM for wild type, G2019S mutant, and drug resistant A2016T mutant LRRK2, respectively, in an
in vitro ATP-site competititon binding assay). While it is shown to inhibit DCLK2 (IC
50 = 45 nM) and suppress MAPK7 autophosphorylation (EC
50 = 160 nM), this compound (<10 μM) demonstrates very good overall selectivity, targeting 12 out of 442 other kinases in a kinase-binding and biochemical assay. At 0.05-3 μM, it induces dose-dependent inhibition of Ser
910 and Ser
935 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 Ser
910 and Ser
935 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.
LRRK2-IN-1 - Calbiochem Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
