Literature DB >> 35707141

Discovery of 1H-Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors.

Robert K Leśniak1,2, R Jeremy Nichols2, Marcus Schonemann2, Jing Zhao2, Chandresh R Gajera2, Grace Lam3, Khanh C Nguyen3, J William Langston2,4, Mark Smith1, Thomas J Montine2.   

Abstract

G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene (LRRK2), a genetic predisposition that is common for Parkinson's disease, as well as for some forms of cancer, and is a shared risk allele for Crohn's disease. GS-LRRK2 has a hyperactive kinase, and although numerous drug discovery programs have targeted LRRK2 kinase, few have reached clinical development. We report the discovery and preliminary development of an entirely novel structural class of potent and selective GS-LRRK2 kinase inhibitors: biaryl-1H-pyrazoles.
© 2022 American Chemical Society.

Entities:  

Year:  2022        PMID： 35707141      PMCID： PMC9190033          DOI： 10.1021/acsmedchemlett.2c00116

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.632


  19 in total

1.  Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: a pooled analysis.

Authors:  Ilir Agalliu; Marta San Luciano; Anat Mirelman; Nir Giladi; Bjorg Waro; Jan Aasly; Rivka Inzelberg; Sharon Hassin-Baer; Eitan Friedman; Javier Ruiz-Martinez; Jose Felix Marti-Masso; Avi Orr-Urtreger; Susan Bressman; Rachel Saunders-Pullman
Journal:  JAMA Neurol       Date:  2015-01       Impact factor: 18.302

2.  Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy.

Authors:  Robert K Leśniak; R Jeremy Nichols; Marcus Schonemann; Jing Zhao; Chandresh R Gajera; William L Fitch; Grace Lam; Khanh C Nguyen; Mark Smith; Thomas J Montine
Journal:  Eur J Med Chem       Date:  2021-12-28       Impact factor: 6.514

3.  14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization.

Authors:  R Jeremy Nichols; Nicolas Dzamko; Nicholas A Morrice; David G Campbell; Maria Deak; Alban Ordureau; Thomas Macartney; Youren Tong; Jie Shen; Alan R Prescott; Dario R Alessi
Journal:  Biochem J       Date:  2010-09-15       Impact factor: 3.857

4.  Selective Inhibitors of G2019S-LRRK2 Kinase Activity.

Authors:  Albert W Garofalo; Jessica Bright; Stéphane De Lombaert; Alyssa M A Toda; Kerry Zobel; Daniele Andreotti; Claudia Beato; Silvia Bernardi; Federica Budassi; Laura Caberlotto; Peng Gao; Cristiana Griffante; Xinying Liu; Luisa Mengatto; Marco Migliore; Fabio Maria Sabbatini; Anna Sava; Elena Serra; Paolo Vincetti; Mingliang Zhang; Holly J Carlisle
Journal:  J Med Chem       Date:  2020-11-16       Impact factor: 7.446

5.  Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-present).

Authors:  Xiao Ding; Feng Ren
Journal:  Expert Opin Ther Pat       Date:  2020-02-18       Impact factor: 6.674

6.  Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease.

Authors:  R Jeremy Nichols; Nicolas Dzamko; Jessica E Hutti; Lewis C Cantley; Maria Deak; Jennifer Moran; Paul Bamborough; Alastair D Reith; Dario R Alessi
Journal:  Biochem J       Date:  2009-10-23       Impact factor: 3.857

7.  Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1).

Authors:  Douglas S Williamson; Garrick P Smith; Pamela Acheson-Dossang; Simon T Bedford; Victoria Chell; I-Jen Chen; Justus C A Daechsel; Zoe Daniels; Laurent David; Pawel Dokurno; Morten Hentzer; Martin C Herzig; Roderick E Hubbard; Jonathan D Moore; James B Murray; Samantha Newland; Stuart C Ray; Terry Shaw; Allan E Surgenor; Lindsey Terry; Kenneth Thirstrup; Yikang Wang; Kenneth V Christensen
Journal:  J Med Chem       Date:  2017-10-27       Impact factor: 7.446

8.  Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease.

Authors:  Ken Y Hui; Heriberto Fernandez-Hernandez; Jianzhong Hu; Adam Schaffner; Nathan Pankratz; Nai-Yun Hsu; Ling-Shiang Chuang; Shai Carmi; Nicole Villaverde; Xianting Li; Manual Rivas; Adam P Levine; Xiuliang Bao; Philippe R Labrias; Talin Haritunians; Darren Ruane; Kyle Gettler; Ernie Chen; Dalin Li; Elena R Schiff; Nikolas Pontikos; Nir Barzilai; Steven R Brant; Susan Bressman; Adam S Cheifetz; Lorraine N Clark; Mark J Daly; Robert J Desnick; Richard H Duerr; Seymour Katz; Todd Lencz; Richard H Myers; Harry Ostrer; Laurie Ozelius; Haydeh Payami; Yakov Peter; John D Rioux; Anthony W Segal; William K Scott; Mark S Silverberg; Jeffery M Vance; Iban Ubarretxena-Belandia; Tatiana Foroud; Gil Atzmon; Itsik Pe'er; Yiannis Ioannou; Dermot P B McGovern; Zhenyu Yue; Eric E Schadt; Judy H Cho; Inga Peter
Journal:  Sci Transl Med       Date:  2018-01-10       Impact factor: 17.956

9.  Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization.

Authors:  Nicolas Dzamko; Maria Deak; Faycal Hentati; Alastair D Reith; Alan R Prescott; Dario R Alessi; R Jeremy Nichols
Journal:  Biochem J       Date:  2010-09-15       Impact factor: 3.857

10.  Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease.

Authors:  Coro Paisán-Ruíz; Shushant Jain; E Whitney Evans; William P Gilks; Javier Simón; Marcel van der Brug; Adolfo López de Munain; Silvia Aparicio; Angel Martínez Gil; Naheed Khan; Janel Johnson; Javier Ruiz Martinez; David Nicholl; Itxaso Martí Carrera; Amets Saénz Pena; Rohan de Silva; Andrew Lees; José Félix Martí-Massó; Jordi Pérez-Tur; Nick W Wood; Andrew B Singleton
Journal:  Neuron       Date:  2004-11-18       Impact factor: 17.173
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