LMTK3 inhibition affects microtubule stability
Chiara Cilibrasi, Angeliki Ditsiou, Athanasios Papakyriakou, George Mavridis, Murat Eravci, Justin Stebbing, Teresa Gagliano, Georgios Giamas
Abstract
<p>C28 induces mitotic arrest in breast cancer cells</p>\n<p><br></p>\n<p>Human lemur tyrosine kinase 3 (LMTK3) is a dual specificity kinase, whose oncogenic role has been well-established in different tumour types, supporting its potential as a therapeutic target [1]. Recently, using robust in vitro and cell-based screening- and selectivity- assays combined with biophysical analyses, we identified a selective small molecule ATP-competitive LMTK3 inhibitor (C28; Fig. 1a) that acts by degrading LMTK3 via the ubiquitin-proteasome pathway. C28 demonstrated effective anticancer effects in a variety of cancer cell lines and in in vivo breast cancer (BC) mouse models [2]. This potent, selective and cell-permeable inhibitor represents an effective tool to investigate and decipher the signalling pathways in which LMTK3 is implicated and progress with our translational research work... </p>