Drug Repurposing of Human LMTK3 from ATP competitive inhibitors for Breast Cancer

Abstract

Breast cancer is the second most common cancer in the world. The ovarian hormone, estrogen plays its role in stimulating breast cell division, breast growth and development and support of the growth of estrogens-responsive tumors. A recently characterized key molecule to breast cancer cell is Lemur tyrosine kinase-3 (LMTK3). LMTK3, belonging to receptor tyrosine kinase family, has been identified as a key protein involved in breast cancer and endocrine resistance. LMTK3 is involved at molecular level for invasion of cells throughout the surrounding tissue, breaching of tissue barrier and permeation of cancer cells using several mechanism. The computational approach is followed for the designing of specific inhibitors against human LMTK3 towards breast cancer treatment. With the use of 3D model of lemur tyrosine kinase3 domain structure and ATP binding site, ATP competitive inhibitors are used to screen the top inhibitors using the AutoDock Vina and AutoDock. The virtual screening and followed by re-docking methods result in identification of Dabrafenib and Axitinib are potent inhibitors for LMTK3 with effective complex formation. Thus, our results reveal the structural mechanism of the LMTK3 inhibition and proposed inhibitors can be used in breast cancer treatment with further experimental study.