Leucine-rich repeat kinase 2 (LRRK2) inhibitors for Parkinson's disease: a patent review of the literature to date

被引:2
|
作者
Morez, Margaux [1 ]
Ordonez, Antonio Jesus Lara [1 ]
Melnyk, Patricia [1 ]
Liberelle, Maxime [1 ]
Lebegue, Nicolas [1 ]
Taymans, Jean-Marc [1 ]
机构
[1] Univ Lille, U1172, LilNCog, Lille Neurosci & Cognit,INSERM,CHU Lille, Lille, France
关键词
LRRK2; kinase; allosteric; GTPase; Parkinson's disease; conformation; ALPHA-SYNUCLEIN; 14-3-3; BINDING; MUTATIONS; G2019S; PHOSPHORYLATION; IDENTIFICATION; DOMAIN; LUNG; ROC;
D O I
10.1080/13543776.2024.2378076
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
IntroductionNearly two decades after leucine rich repeat kinase 2 (LRRK2) was discovered as a genetic determinant of Parkinson's disease (PD), LRRK2 has emerged a priority therapeutic target in PD and inhibition of its activity is hypothesized to be beneficial.Areas coveredLRRK2 targeting agents, in particular kinase inhibitors and agents reducing LRRK2 expression show promise in model systems and have progressed to phase I and phase II clinical testing for PD. Several additional targeting strategies for LRRK2 are emerging, based on promoting specific 'healthy' LRRK2 quaternary structures, heteromeric complexes and conformations.Expert opinionIt can be expected that LRRK2 targeting strategies may proceed to phase III clinical testing for PD in the next five years, allowing the field to discover the real clinical value of LRRK2 targeting strategies.
引用
收藏
页码:773 / 788
页数:16
相关论文
共 50 条
  • [11] The development of inhibitors of leucine-rich repeat kinase 2 (LRRK2) as a therapeutic strategy for Parkinson's disease: the current state of play
    Azeggagh, Sonia
    Berwick, Daniel C.
    BRITISH JOURNAL OF PHARMACOLOGY, 2022, 179 (08) : 1478 - 1495
  • [12] Dependence of Leucine-rich Repeat Kinase 2 (LRRK2) Kinase Activity on Dimerization
    Sen, Saurabh
    Webber, Philip J.
    West, Andrew B.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (52) : 36346 - 36356
  • [13] Chemical Biology of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors
    Estrada, Anthony A.
    Sweeney, Zachary K.
    JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (17) : 6733 - 6746
  • [14] Recent Update on the Development of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors: A Promising Target for the Treatment of Parkinson's Disease
    Patel, Ashish
    Patel, Stuti
    Mehta, Meshwa
    Patel, Yug
    Langaliya, Dhruv
    Bhalodiya, Shyam
    Bambharoliya, Tushar
    MEDICINAL CHEMISTRY, 2022, 18 (07) : 757 - 771
  • [15] Effect of leucine-rich repeat kinase 2 (LRRK2) on protein synthesis
    Kim, Hyejung
    Son, Ilhong
    Seol, Wongi
    ANIMAL CELLS AND SYSTEMS, 2018, 22 (01) : 15 - 21
  • [16] A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls
    Vissers, Maurits F. J. M.
    Troyer, Matthew D.
    Thijssen, Eva
    Heuberger, Jules A. A. C.
    Groeneveld, Geert Jan
    Huntwork-Rodriguez, Sarah
    CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 2023, 16 (08): : 1408 - 1420
  • [17] Leucine-rich repeat kinase 1: a paralog of LRRK2 and a candidate gene for Parkinson’s disease
    Julie P. Taylor
    Mary M. Hulihan
    Jennifer M. Kachergus
    Heather L. Melrose
    Sarah J. Lincoln
    Kelly M. Hinkle
    Jeremy T. Stone
    Owen A. Ross
    Robert Hauser
    Jan Aasly
    Thomas Gasser
    Haydeh Payami
    Zbigniew K. Wszolek
    Matthew J. Farrer
    Neurogenetics, 2007, 8 : 95 - 102
  • [18] Leucine-rich repeat kinase 2 and Parkinson's disease
    Kang, Un-Beom
    Marto, Jarrod A.
    PROTEOMICS, 2017, 17 (1-2)
  • [19] Leucine-rich repeat kinase 1:: a paralog of LRRK2 and a candidate gene for Parkinson's disease
    Taylor, Julie P.
    Hulihan, Mary M.
    Kachergus, Jennifer M.
    Melrose, Heather L.
    Lincoln, Sarah J.
    Hinkle, Kelly M.
    Stone, Jeremy T.
    Ross, Owen A.
    Hauser, Robert
    Aasly, Jan
    Gasser, Thomas
    Payami, Haydeh
    Wszolek, Zbigniew K.
    Farrer, Matthew J.
    NEUROGENETICS, 2007, 8 (02) : 95 - 102
  • [20] Development of Inducible Leucine-rich Repeat Kinase 2 (LRRK2) Cell Lines for Therapeutics Development in Parkinson's Disease
    Huang, Liang
    Shimoji, Mika
    Wang, Juan
    Shah, Salim
    Kamila, Sukanta
    Biehl, Edward R.
    Lim, Seung
    Chang, Allison
    Maguire-Zeiss, Kathleen A.
    Su, Xiaomin
    Federoff, Howard J.
    NEUROTHERAPEUTICS, 2013, 10 (04) : 840 - 851