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LRRK2-IN-1

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Chemical Structure| 1234480-84-2 同义名 : Leucine-rich repeat kinase 2 IN-1
CAS号 : 1234480-84-2
货号 : A281167
分子式 : C31H38N8O3
纯度 : 99%+
分子量 : 570.685
MDL号 : MFCD22683805
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(52.57 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 13 mg/mL suspension

生物活性
靶点

  • LRRK2

    LRRK2 (WT), IC50:13 nM

    LRRK2 (G2019S), IC50:6 nM
描述 Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene is tightly linked to Parkinson’s disease (PD) as its missense mutation, G2019S, is frequently found in not only familial but also sporadic PD. LRRK-2IN1 inhibits both wild-type and G2019S mutant LRRK2 kinase activity with IC50 values of 13 nM and 6 nM, respectively[4]. LRRK2-IN-1 at 100 nM and 500 nM could protect against G2019S-associated cellular toxicity and significantly improve cell survival in human SH-SY5Y neuroblastoma cell line transfected with G2019S -LRRK2 along. It was also found that treatment of LRRK2-IN1 during both pre- and post-symptomatic stages significantly protect dopamine neurons against neurodegeneration caused by G2019S in C. elegans [5]. AsPC-1 cells treated with 0.5 μM- and 5.0 μM-LRRK2-IN-1 showed decreased expression of epithelial-to-mesenchymal transition (EMT) factors and WNT1, increased expression of E-cadherin. Consistently, there was a dose-dependent reduction in the invasive potential of AsPC-1 cells 24 h post LRRK2-IN-1 treatment, with an approximately 70% decrease in invasive potential following 5 μM treatment. AsPC-1 tumor xenografts injected with LRRK2-IN-1(100 mg/kg, 4weeks) showed more than 50% decreases in tumor volume and weight[6].
作用机制 LRRK2-IN-1 inhibits wild-type and G2019S mutant LRRK2 kinase in an ATP-competitive manner.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293 cells Function assay Inhibition of LRRK2 G2019S mutant expressed in HEK293 cells using nictide and ATP as substrate, IC50=0.006 μM 22335897
HEK293 cells 0.03-3 μM Function assay 90 mins Inhibition of wild-type LRRK2 phosphorylation at Ser935 expressed in HEK293 cells at 0.03 to 3 uM after 90 mins by immunoblot analysis 22335897
lymphoblastoid cells 0.03 to 3 uM Function assay 90 mins Inhibition of LRRK2 in human lymphoblastoid cells assessed as inhibition of Ser910 autophosphorylation at 0.03 to 3 uM after 90 mins by immunoblot method 22863203
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.18mL

8.76mL

1.75mL

0.88mL

17.52mL

3.50mL

1.75mL
参考文献

[1]Yao C, Johnson WM, et al. Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity. Hum Mol Genet. 2013 Jan 15;22(2):328-44.

[2]Deng X, Dzamko N, et al. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat Chem Biol. 2011 Apr;7(4):203-5.

[3]Atashrazm F, Dzamko N, et al. LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives. Clin Pharmacol. 2016 Oct 20;8:177-189. eCollection 2016.

[4]Deng X, Dzamko N, Prescott A, Davies P, Liu Q, Yang Q, Lee JD, Patricelli MP, Nomanbhoy TK, Alessi DR, Gray NS. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat Chem Biol. 2011 Apr;7(4):203-5. doi: 10.1038/nchembio.538. Epub 2011 Mar 6. PMID: 21378983; PMCID: PMC3287420.

[5]Yao C, Johnson WM, Gao Y, Wang W, Zhang J, Deak M, Alessi DR, Zhu X, Mieyal JJ, Roder H, Wilson-Delfosse AL, Chen SG. Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity. Hum Mol Genet. 2013 Jan 15;22(2):328-44. doi: 10.1093/hmg/dds431. Epub 2012 Oct 12. PMID: 23065705; PMCID: PMC3526163.

[6]Weygant N, Qu D, Berry WL, May R, Chandrakesan P, Owen DB, Sureban SM, Ali N, Janknecht R, Houchen CW. Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1. Mol Cancer. 2014 May 6;13:103. doi: 10.1186/1476-4598-13-103. PMID: 24885928; PMCID: PMC4030036.