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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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 Ataxia Telangiectasia Mutated Protein in Cancer Therapy
Current Drug Targets A Medicinal Chemist’s Perspective Towards Structure Activity Relationship of Heterocycle Based Anticancer Agents
Current Topics in Medicinal Chemistry Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, their Niche and Targeted Therapy
Current Stem Cell Research & Therapy The Effects of Cantharidin and Cantharidin Derivates on Tumour Cells
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot Topic: Beyond Chemotherapy: Future Directions in Lymphoma Treatment (Guest Editor: Thomas Decker)]
Current Drug Targets Biology of Protooncogene c-kit Receptor and Spermatogenesis
Current Pharmacogenomics miRNAs in Gastrointestinal and Liver Cancers: Their Perspectives and Clinical Applications
Current Pharmaceutical Design Whole Cell Biocatalysts for the Preparation of Nucleosides and their Derivatives
Current Pharmaceutical Design Src Family Kinases as Potential Therapeutic Targets for Malignancies and Immunological Disorders
Current Medicinal Chemistry Epratuzumab and Blinatumomab as Therapeutic Antibodies for Treatment of Pediatric Acute Lymphoblastic Leukemia: Current Status and Future Perspectives
Current Medicinal Chemistry Nuclear Export Mediated Regulation of MicroRNAs: Potential Target for Drug Intervention
Current Drug Targets Therapeutic Applications of Mesenchymal Stem Cells: A Comprehensive Review
Current Stem Cell Research & Therapy Targeting Ion Channels in Leukemias: A New Challenge for Treatment
Current Medicinal Chemistry Spirocyclic Nucleosides in Medicinal Chemistry: An Overview
Mini-Reviews in Medicinal Chemistry FAK and Nanog Cross Talk with p53 in Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Selection of Active Antiviral Compounds Against COVID-19 Disease Targeting Coronavirus Endoribonuclease Nendou/NSP15 Via Ligandbased Virtual Screening and Molecular Docking
Letters in Drug Design & Discovery Mitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy
Current Medicinal Chemistry Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil
Current Cancer Drug Targets Hypoxia-Inducible Factors and Sphingosine 1-Phosphate Signaling
Anti-Cancer Agents in Medicinal Chemistry In Vitro Antitumoral Activity of Palladium(II) and Platinum(II) Complexes with O,O'-Dialkyl Esters of Ethylene-bis(S)-Leucine
Letters in Drug Design & Discovery