University of Sussex
Browse
ijms-24-00865 (1).pdf (4.76 MB)

The inhibitory properties of a novel, selective LMTK3 kinase inhibitor

Download (4.76 MB)
journal contribution
posted on 2023-06-10, 05:57 authored by Alessandro AgnarelliAlessandro Agnarelli, Andrea Lauer BetranAndrea Lauer Betran, Athanasios Papakyriakou, Viviana Vella, Mark SamuelsMark Samuels, Panagiotis Papanastasopoulos, Christina Giamas, Erika J Mancini, Justin Stebbing, John SpencerJohn Spencer, Chiara Cilibrasi, Angeliki Ditsiou, Georgios GiamasGeorgios Giamas
Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5'-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy.

History

Publication status

  • Published

File Version

  • Published version

Journal

International Journal of Molecular Sciences

ISSN

1661-6596

Publisher

MDPI AG

Issue

1

Volume

24

Page range

e865 1-15

Department affiliated with

  • Biochemistry Publications

Institution

University of Sussex

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2023-01-12

First Open Access (FOA) Date

2023-01-12

First Compliant Deposit (FCD) Date

2023-01-12

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC