Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
27 10 2022
Historique:
pubmed: 8 10 2022
medline: 29 10 2022
entrez: 7 10 2022
Statut: ppublish

Résumé

LIM domain kinases 1 and 2 (LIMK1 and LIMK2) regulate actin dynamics and subsequently key cellular functions such as proliferation and migration. LIMK1 and LIMK2 phosphorylate and inactivate cofilin leading to increased actin polymerization. As a result, LIMK inhibitors are emerging as a promising treatment strategy for certain cancers and neurological disorders. High-quality chemical probes are required if the role of these kinases in health and disease is to be understood. To that end, we report the results of a comparative assessment of 17 reported LIMK1/2 inhibitors in a variety of

Identifiants

pubmed: 36205722
doi: 10.1021/acs.jmedchem.2c00751
pmc: PMC9619402
doi:

Substances chimiques

Actin Depolymerizing Factors 0
Actins 0
Lim Kinases EC 2.7.11.1
LIMKi3 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13705-13713

Subventions

Organisme : Medical Research Council
ID : MR/S005331/1
Pays : United Kingdom

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Auteurs

Ross Collins (R)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Hyunah Lee (H)

Centre for Medicines Discovery, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

D Heulyn Jones (DH)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Jonathan M Elkins (JM)

Centre for Medicines Discovery, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Jason A Gillespie (JA)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Carys Thomas (C)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Alex G Baldwin (AG)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Kimberley Jones (K)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Loren Waters (L)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Marie Paine (M)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

John R Atack (JR)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Simon E Ward (SE)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

Olivera Grubisha (O)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

David W Foley (DW)

Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.

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Classifications MeSH