Computational and Biological Investigations on Abl1 Tyrosine Kinase: A Review

Abstract

Abl1 tyrosine kinase is a validated target for the treatment of chronic myeloid leukemia. It is a form of cancer that is difficult to treat and much research is being done to identify new molecular entities and to tackle drug resistance is-sues. In recent years, drug resistance of Abl1 tyrosine kinase has become a major healthcare concern. Second and third generation TKI reported better responses against the resistant forms, still they had no impact on long term survival pro-longation. New compounds derived from natural products and organic small molecule inhibitors can lay the foundation for better clinical therapies in the future. Computational methods, experimental and biological studies can help us under-stand the mechanism of drug resistance and identify novel molecule inhibitors. ADMET parameters analysis of reported drugs and novel small molecule inhibitors can also provide valuable insight. In this review, available therapies, point mu-tations, structure-activity relationship and ADMET parameters of reported series of Abl1 tyrosine kinase inhibitors and drugs are summarised. We summarise in detail recent computational and molecular biology studies that focus on design-ing drug molecules, investigation of natural product compounds and organic new chemical entities. Current ongoing re-search suggests that selective targeting of Abl1 tyrosine kinase at the molecular level to combat drug resistance in chronic myeloid leukemia is promising.