Abstract
Since protein kinases are frequently mutated or otherwise deregulated in human malignancies, they serve as a target for differentiating between tumor cells and normal tissues. Imatinib mesylat (IM), an inhibitor of the BCR-ABL tyrosine kinase was introduced in 2001 and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Since 2005 a second generation of tyrosine kinase inhibitors is to follow in Imatinibs footsteps: The development of these new small molecules was promoted by the identification of potential target kinases within the cellular signaling apparatus. Modern biochemical tools provide relevant amounts of these target kinases necessary for high throughput screening (HTS) campaigns and for elucidation of their 3-D structure by crystallography. Supported by computational chemistry the resulting data have enabled rational drug design. In this review low molecular weight inhibitors used for the CML treatment are summarized, pointing out their chemical similarities and differences.
Keywords: CML, Imatinib, aurora kinase, BCR-ABL, SGX393, tyrosine kinase inhibitor
Current Pharmaceutical Design
Title: Imatinib and Its Successors – How Modern Chemistry has Changed Drug Development
Volume: 15 Issue: 2
Author(s): Bernhard A. Muller
Affiliation:
Keywords: CML, Imatinib, aurora kinase, BCR-ABL, SGX393, tyrosine kinase inhibitor
Abstract: Since protein kinases are frequently mutated or otherwise deregulated in human malignancies, they serve as a target for differentiating between tumor cells and normal tissues. Imatinib mesylat (IM), an inhibitor of the BCR-ABL tyrosine kinase was introduced in 2001 and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Since 2005 a second generation of tyrosine kinase inhibitors is to follow in Imatinibs footsteps: The development of these new small molecules was promoted by the identification of potential target kinases within the cellular signaling apparatus. Modern biochemical tools provide relevant amounts of these target kinases necessary for high throughput screening (HTS) campaigns and for elucidation of their 3-D structure by crystallography. Supported by computational chemistry the resulting data have enabled rational drug design. In this review low molecular weight inhibitors used for the CML treatment are summarized, pointing out their chemical similarities and differences.
Export Options
About this article
Cite this article as:
Muller A. Bernhard, Imatinib and Its Successors – How Modern Chemistry has Changed Drug Development, Current Pharmaceutical Design 2009; 15 (2) . https://dx.doi.org/10.2174/138161209787002933
DOI https://dx.doi.org/10.2174/138161209787002933 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
An Antileukemic Glutaminase Free L-Asparaginase from Bacillus brevis
Current Biotechnology Lead Generation for Human Mitotic Kinesin Eg5 Using Structure-based Virtual Screening and Validation by In-vitro and Cell-based Assays
Current Computer-Aided Drug Design Recent Advances in the Development of Selective Mcl-1 Inhibitors for the Treatment of Cancer (2017-Present)
Recent Patents on Anti-Cancer Drug Discovery Tackling COVID-19 Through Ayurveda: A Review on the Herbs of Recommended Indian Remedies
Current Traditional Medicine The Endocannabinoid System in Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells
Current Pharmaceutical Biotechnology Honey as a Source of Dietary Antioxidants: Structures, Bioavailability and Evidence of Protective Effects Against Human Chronic Diseases
Current Medicinal Chemistry Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy
Anti-Cancer Agents in Medicinal Chemistry The Current Chemical Utility of Marine and Terrestrial Filamentous Fungi in Side-Chain Chemistry
Current Organic Chemistry Brain Tumor-Related Epilepsy
Current Neuropharmacology The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy A New Synthetic Spiroketal: Studies on Antitumor Activity on Murine Melanoma Model In Vivo and Mechanism of Action In Vitro
Anti-Cancer Agents in Medicinal Chemistry The Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification
Current Pharmaceutical Design The Therapeutical Potential of a Novel Pterocarpanquinone LQB-118 to Target Inhibitor of Apoptosis Proteins in Acute Myeloid Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry The Use of Structural Biology in Janus Kinase Targeted Drug Discovery
Current Drug Targets The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders
Current Drug Targets The Tribbles-1 Protein in Humans: Roles and Functions in Health and Disease
Current Molecular Medicine N-Hydroxyguanidines as Substrates of Nitric Oxide Synthases
Current Topics in Medicinal Chemistry A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections
Current Pharmaceutical Design