1. The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor
- Author
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Alessandro Agnarelli, Andrea Lauer Betrán, Athanasios Papakyriakou, Viviana Vella, Mark Samuels, Panagiotis Papanastasopoulos, Christina Giamas, Erika J. Mancini, Justin Stebbing, John Spencer, Chiara Cilibrasi, Angeliki Ditsiou, and Georgios Giamas
- Subjects
LMTK3 ,kinase inhibitor ,breast cancer ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - 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.
- Published
- 2023
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