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

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

  • J Med Chem. 2022 Oct 27;65(20):13705-13713. doi: 10.1021/acs.jmedchem.2c00751.
Ross Collins 1,  Hyunah Lee 2,  D Heulyn Jones 1,  Jonathan M Elkins 2,  Jason A Gillespie 1,  Carys Thomas 1,  Alex G Baldwin 1,  Kimberley Jones 1,  Loren Waters 1,  Marie Paine 1,  John R Atack 1,  Simon E Ward 1,  Olivera Grubisha 1,  David W Foley 1
Affiliations

Affiliations

  • 1 Medicines Discovery Institute, School of Biosciences, Cardiff University, Cardiff CF10 3AT, United Kingdom.
  • 2 Centre for Medicines Discovery, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
PMID: 36205722 DOI: 10.1021/acs.jmedchem.2c00751
Abstract

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 in vitro enzymatic and cellular assays. Our evaluation has identified three compounds (TH-257, LIJTF500025, and LIMKi3) as potent and selective inhibitors suitable for use as in vitro and in vivo pharmacological tools for the study of LIMK function in Cell Biology.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z