1. Autophagy
  2. LRRK2
  3. RN341

RN341 is a specific type II kinase inhibitor of LRRK2 (IC50: 296 nM). RN341 inhibits LRRK2 phosphorylation and avoids S935 dephosphorylation by stabilizing the open conformation. RN341 rescues LRRK2-mediated kinesin motility block by preventing microtubule binding. RN341 effectively inhibits LRRK2 wild-type and G2019S mutant at the cellular level. RN341 provides a new direction for Parkinson's disease research.

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RN341

RN341 Chemical Structure

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Description

RN341 is a specific type II kinase inhibitor of LRRK2 (IC50: 296 nM). RN341 inhibits LRRK2 phosphorylation and avoids S935 dephosphorylation by stabilizing the open conformation. RN341 rescues LRRK2-mediated kinesin motility block by preventing microtubule binding. RN341 effectively inhibits LRRK2 wild-type and G2019S mutant at the cellular level. RN341 provides a new direction for Parkinson's disease research[1].

In Vitro

RN341 (Compound IRN341) (0.25-10 μM, 4 h) specifically inhibits substrate phosphorylation of LRRK1/2 but does not affect the biomarker site S935[1].
RN341 (1-10 μM) inhibits the residual activity of 10 kinases to less than 30 % at high concentrations, as shown in an activity screening of 350 kinases[1].
RN341 (0.01-10 μM) shows EC50 values indicating that, among the 12 identified off-target kinases, only 4 (STK10, MAPK14, JNK2, and TTK) are inhibited, with EC50s in the low micromolar range (<5 μM)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: 293T cells (transfected with LRRK1 and its substrate Rab7), 293T cells (co-transfected with LRRK2 and GFP-Rab8a), 293T cells (transfected with GFP-Rab8a and either wild-type or G2019S LRRK2), 293T cells (transiently co-transfected with LRRK1 and its substrate GFP-Rab7), 293T cells (transiently co-transfected with GFP-Rab8a and either GFP-11 tagged wild-type (WT) or GFP-11 tagged G2019S LRRK2)
Concentration: 0.25 μM, 0.5 μM, 1 μM, 2.5 μM, 5 μM, 10 μM
Incubation Time: 4 h
Result: Showed strong inhibitory effects on LRRK1 kinase activity, which in turn inhibited Rab7 S72 phosphorylation.
Inhibited LRRK2-mediated Rab8a phosphorylation in a dose-dependent manner.
Did not reduce LRRK2 biomarker site S935 phosphorylation.
Molecular Weight

554.71

Formula

C30H34N8OS

SMILES

O=C(NC1=CC(C(C)(C)C)=NN1C2=CC=C(C)C=C2)NC3=CC(C4=CNC5=NC(SCC)=NC(NC)=C54)=CC=C3

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Room temperature in continental US; may vary elsewhere.

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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RN341
Cat. No.:
HY-174427
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