Title:Computational and Biological Investigations on Abl1 Tyrosine Kinase: A Review
VOLUME: 22 ISSUE: 1
Author(s):Masilamani Elizabeth Sobhia*, G. Siva Kumar, Antara Mallick, Harmanpreet Singh, Kranthi Kumar, Meenakshi Chaurasiya, Monica Singh, Narendra Gera, Sindhuja Deverakonda and Vinay Baghel
Affiliation:Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar
Keywords:Abl1 tyrosine kinase, Chronic myeloid leukemia, ADMET properties, Drug resistance, 3D-QSAR, Molecular docking,
Molecular dynamics, Biological inhibitory studies.
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 issues. 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 prolongation.
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 understand 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 insights. In this review, available therapies, point mutations,
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 designing drug molecules, investigation of natural product compounds
and organic new chemical entities. Current ongoing research suggests that selective targeting of
Abl1 tyrosine kinase at the molecular level to combat drug resistance in chronic myeloid leukemia
is promising.
