Structure-Based Optimization of Pyrazolo[3,4-d]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines
- 8 February 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 51 (5), 1252-1259
- https://doi.org/10.1021/jm701240c
Abstract
Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and antiproliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward AblKeywords
This publication has 23 references indexed in Scilit:
- Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML)Critical Reviews in Oncology/Hematology, 2006
- Characterization of AMN107, a selective inhibitor of native and mutant Bcr-AblCancer Cell, 2005
- A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistanceProceedings of the National Academy of Sciences of the United States of America, 2005
- Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr–Abl signal transduction and oncogenesisOncogene, 2002
- Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapyLeukemia, 2002
- Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or AmplificationScience, 2001
- Chronic Myeloid LeukemiaThe New England Journal of Medicine, 1999
- Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cellsNature Medicine, 1996
- Tyrosine Kinase Activity and Transformation Potency of bcr-abl Oncogene ProductsScience, 1990
- A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa StainingNature, 1973