Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disease originating from a constitutively active tyrosine kinase, called BCR-ABL, expressed by an oncogene resulting from a reciprocal translocation between chromosome 9 and chromosome 22, coded as (t[9,22][q34;q11]). Inhibition of BCR-ABL with tyrosine kinase inhibitors (TKI) proved to be an efficient targeted therapy of Philadelphia-positive (Ph+) CML in the chronic phase. This review mainly addresses the synthetic pathways and process chemistry leading to the large scale preparation for pre-clinical demands and clinical supply of the three TKIs approved for Ph+ CML, i.e., imatinib, dasatinib and nilotinib and three more investigational drugs, i.e., bosutinib, ponatinib and bafetinib. Recent progress on the biochemical profiling of the six examined TKIs has been also reported.
Keywords: Chronic myeloid leukemia, BCR-ABL, tyrosine kinase inhibitors, T315I mutation, process chemistry
Current Medicinal Chemistry
Title: BCR-ABL Inhibitors in Chronic Myeloid Leukemia: Process Chemistry and Biochemical Profile
Volume: 18 Issue: 19
Author(s): F. Leonetti, A. Stefanachi, O. Nicolotti, M. Catto, L. Pisani, S. Cellamare and A. Carotti
Affiliation:
Keywords: Chronic myeloid leukemia, BCR-ABL, tyrosine kinase inhibitors, T315I mutation, process chemistry
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease originating from a constitutively active tyrosine kinase, called BCR-ABL, expressed by an oncogene resulting from a reciprocal translocation between chromosome 9 and chromosome 22, coded as (t[9,22][q34;q11]). Inhibition of BCR-ABL with tyrosine kinase inhibitors (TKI) proved to be an efficient targeted therapy of Philadelphia-positive (Ph+) CML in the chronic phase. This review mainly addresses the synthetic pathways and process chemistry leading to the large scale preparation for pre-clinical demands and clinical supply of the three TKIs approved for Ph+ CML, i.e., imatinib, dasatinib and nilotinib and three more investigational drugs, i.e., bosutinib, ponatinib and bafetinib. Recent progress on the biochemical profiling of the six examined TKIs has been also reported.
Export Options
About this article
Cite this article as:
Leonetti F., Stefanachi A., Nicolotti O., Catto M., Pisani L., Cellamare S. and Carotti A., BCR-ABL Inhibitors in Chronic Myeloid Leukemia: Process Chemistry and Biochemical Profile, Current Medicinal Chemistry 2011; 18 (19) . https://dx.doi.org/10.2174/092986711796150414
DOI https://dx.doi.org/10.2174/092986711796150414 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Targeting the Acute Myeloid Leukemia Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Fragment-Based Discovery of Inhibitors of Protein Kinase B
Current Topics in Medicinal Chemistry Engineered Nanoparticles Against MDR in Cancer: The State of the Art and its Prospective
Current Pharmaceutical Design Chemoprevention of Colorectal Cancer: Ready for Routine Use?
Current Topics in Medicinal Chemistry Acute Myeloid Leukemia in the Elderly: Current Therapeutic Results and Perspectives for Clinical Research
Reviews on Recent Clinical Trials Stereoselective Metabolic and Pharmacokinetic Analysis of the Chiral Active Components from Herbal Medicines
Current Pharmaceutical Analysis Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation
Current Stem Cell Research & Therapy Cytochrome P450 Gene Polymorphism and Cancer
Current Drug Metabolism Gene Transfer and Drug Delivery with Electric Pulse Generators
Current Drug Metabolism Cytotoxic Nucleoside Analogues: Different Strategies to Improve their Clinical Efficacy
Current Medicinal Chemistry Animal Modeling of Cancer Pathology and Studying Tumor Response to Therapy
Current Drug Targets Acute Graft-Versus-Host Disease-Challenge for a Broader Application of Allogeneic Hematopoietic Cell Transplantation
Current Stem Cell Research & Therapy Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?
Current Drug Targets Monoclonal Antibodies in the Treatment of Multiple Sclerosis
Current Medicinal Chemistry Plant Cells as Pharmaceutical Factories
Current Pharmaceutical Design Morpho-Functional Features of In-Vitro Cell Death Induced by Physical Agents
Current Pharmaceutical Design Genomic Signatures for Individualized Treatment of Malignant Tumors
Current Drug Discovery Technologies FOXO and FOXM1 in Cancer: The FOXO-FOXM1 Axis Shapes the Outcome of Cancer Chemotherapy
Current Drug Targets The Role of Tumor Suppressor DLC-1: Far From Clear
Anti-Cancer Agents in Medicinal Chemistry Electrocatalytic Determination of 6-Mercaptopurine Using Multiwall Carbon Nanotubes Paste Electrode in the Presence of Methyldopa
Current Nanoscience