The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer
therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology …

For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and
acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell …

Background Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1
protein, locking BCR-ABL1 into an inactive conformation through a mechanism distinct from …

Proteins often undergo large conformational changes when binding small molecules, but
atomic-level descriptions of such events have been elusive. Here, we report unguided …

INTRODUCTION Protein kinases mediate many cell signaling processes. Central to their
physiological function is the regulation of their binding and enzymatic activities, which is …

Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme
deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy …

Over the past decade, covalent kinase inhibitors (CKI) have seen a resurgence in drug
discovery. Covalency affords a unique set of advantages as well as challenges relative to …

Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine
kinase inhibitor to be discovered with high specificity for Bcr-Abl protein resulting from t (9 …

Phenotypic and functional heterogeneity arise among cancer cells within the same tumour
as a consequence of genetic change, environmental differences and reversible changes in …

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by a reciprocal
translocation [t (9; 22)(q34; q11. 2)] that leads to the fusion of ABL1 gene sequences (9q34) …