Virtual screening of large-scale small molecule libraries against bruton tyrosine kinase effective in chronic lymphocytic leukaemia

Bruton Tyrosine Kinases (BTKs) are known to play a role in Chronic Lymphotic Leukemia (CLL), Waldenström Macroglobulinemia, Marginal Zone Lymphoma, Mantle Cell Lymphoma (MCL), and Graft Versus Host diseases. BTKs are a family of Tyrosine Kinases that are involved in signal transduction of B lymphocytes, development and maturation of B lymphocytes. Overexpression of B cells causes cancer. BTKs are critical in the activation of the B-Cell Receptor (BCR) signaling pathway. Blocking the activation of BTKs in this part may be promising for the treatment of Chronic Lymphocytic Leukemia. Therefore, in this study, we focus on identifying small molecule therapeutics targeting the Human Bruton Tyrosine Kinase. We use the Ibrutinib molecule, which is known to inhibit BTKs, as a query molecule. IUPAC text files of molecular fragments in Ibrutinib were used to screen 5 different libraries containing small molecules. More than 2 million molecules were scanned. We performed Covalent Docking experiments on our molecules obtained by Text Mining. In this context, it is aimed to discover hit molecules that will prevent BTKs with virtual scanning algorithms.