The inhibitory properties of a novel, selective LMTK3 kinase inhibitor

Agnarelli, Alessandro, Lauer Betran, Andrea, Papakyriakou, Athanasios, Vella, Viviana, Samuels, Mark, Papanastasopoulos, Panagiotis, Giamas, Christina, Mancini, Erika J, Stebbing, Justin, Spencer, John, Cilibrasi, Chiara, Ditsiou, Angeliki and Giamas, Georgios (2023) The inhibitory properties of a novel, selective LMTK3 kinase inhibitor. International Journal of Molecular Sciences, 24 (1). e865 1-15. ISSN 1661-6596

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Abstract

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.

Item Type: Article
Keywords: Cancer, Breast Cancer, Pharmaceuticals, Cancer
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Chemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 12 Jan 2023 14:08
Last Modified: 12 Jan 2023 14:15
URI: http://sro.sussex.ac.uk/id/eprint/110115

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