The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor

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.

Automated summary

Recently, the oncogenic role of LMTK3 has been established in different tumors, making it a potential target for cancer therapy. In this study, a highly specific small molecule inhibitor for LMTK3, called C36, was identified and shown to have significant therapeutic effects in cancer cell lines. The binding affinity between LMTK3 and C36 was demonstrated through microscale thermophoresis, and C36 was found to inhibit the activity of LMTK3 by binding to both the ATP- and substrate-binding sites. Treatment with C36 led to decreased proliferation and increased apoptosis in breast cancer cells, highlighting the potential of LMTK3 inhibitors for cancer therapy.