Abstract
The TGFβ type I receptor kinase (ALK5) is an attractive target for intervention in TGFβ signaling due to its druggability as well as its centrality and specificity in the pathway. A number of potent, selective ALK5 inhibitors have been discovered which interact with the ATP-binding site of ALK5. Crystallographic studies of these molecules bound to ALK5 have provided an understanding of potency and selectivity achieved by these inhibitors. ALK5 kinase inhibitors are potently active in models of cancer due to mechanisms of action similar to those for other TGFβ inhibitory agents. Recent insights into the function of TGFβ in human tumors as well as in preclinical models of cancer are helping to identify potential target patient populations and drug combinations for the development of ALK5 kinase inhibitors and other TGFβ- targeted therapeutics. Differences in the toxicological effects, pharmacokinetics and clinical side effects of ALK5 kinase inhibitors and other TGFβ-targeted agents provide a useful and differentiated set of TGFβ signaling inhibitory agents to investigate in clinical studies.
Keywords: Transforming growth factor-β, Cancer, Transforming growth factor-β type I receptor kinase inhibitor, Activin receptor-like kinase 5 inhibitor, ALK5 inhibitor, Transforming growth factor-β receptor kinase inhibitor, human tumors, Smad-mediated gene expression, clinical trials, targeted therapies, ALK5 small molecule binding pockets, Smad signaling, kinase inhibitors, hydrophobic back pocket, hydrogen bond
Current Pharmaceutical Biotechnology
Title: TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology
Volume: 12 Issue: 12
Author(s): Leona E. Ling and Wen-Cherng Lee
Affiliation:
Keywords: Transforming growth factor-β, Cancer, Transforming growth factor-β type I receptor kinase inhibitor, Activin receptor-like kinase 5 inhibitor, ALK5 inhibitor, Transforming growth factor-β receptor kinase inhibitor, human tumors, Smad-mediated gene expression, clinical trials, targeted therapies, ALK5 small molecule binding pockets, Smad signaling, kinase inhibitors, hydrophobic back pocket, hydrogen bond
Abstract: The TGFβ type I receptor kinase (ALK5) is an attractive target for intervention in TGFβ signaling due to its druggability as well as its centrality and specificity in the pathway. A number of potent, selective ALK5 inhibitors have been discovered which interact with the ATP-binding site of ALK5. Crystallographic studies of these molecules bound to ALK5 have provided an understanding of potency and selectivity achieved by these inhibitors. ALK5 kinase inhibitors are potently active in models of cancer due to mechanisms of action similar to those for other TGFβ inhibitory agents. Recent insights into the function of TGFβ in human tumors as well as in preclinical models of cancer are helping to identify potential target patient populations and drug combinations for the development of ALK5 kinase inhibitors and other TGFβ- targeted therapeutics. Differences in the toxicological effects, pharmacokinetics and clinical side effects of ALK5 kinase inhibitors and other TGFβ-targeted agents provide a useful and differentiated set of TGFβ signaling inhibitory agents to investigate in clinical studies.
Export Options
About this article
Cite this article as:
E. Ling Leona and Lee Wen-Cherng, TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology, Current Pharmaceutical Biotechnology 2011; 12 (12) . https://dx.doi.org/10.2174/138920111798808257
DOI https://dx.doi.org/10.2174/138920111798808257 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
Latest Advancements in Biotherapeutics
The scope of this thematic issue is to comprehensively explore the rapidly evolving landscape of biotherapeutics, emphasizing breakthroughs in precision medicine. Encompassing diverse therapeutic modalities, the issue will delve into the latest developments in monoclonal antibodies, CRISPR/Cas gene editing, CAR-T cell therapies, and innovative drug delivery systems, such as nanoparticle-based ...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
Related Articles
-
The Role of Histone Demethylase GASC1 in Cancer and its Therapeutic Potential
Current Cancer Therapy Reviews α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease
Current Alzheimer Research Molecular Targets of FTY720 (Fingolimod)
Current Molecular Medicine Looking out for Cancer Stem Cells’ Properties: The Value-Driving Role of CD44 for Personalized Medicines
Current Cancer Drug Targets BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK
Anti-Cancer Agents in Medicinal Chemistry Immunotherapy of Malignant Gliomas Using Autologous and Allogeneic Tissue Cells
Anti-Cancer Agents in Medicinal Chemistry NUPR1 Interacts with p53, Transcriptionally Regulates p21 and Rescues Breast Epithelial Cells from Doxorubicin-Induced Genotoxic Stress
Current Cancer Drug Targets In Situ Gene Therapy for Prostate Cancer
Current Gene Therapy Clinical Importance and Potential Use of Small Molecule Inhibitors of Focal Adhesion Kinase
Anti-Cancer Agents in Medicinal Chemistry DNA Drug Design for Cancer Therapy
Current Pharmaceutical Design Ceramide-Based Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Rho as a Target to Promote Repair: Translation to Clinical Studies with Cethrin
Current Pharmaceutical Design Cannabinoids: Between Neuroprotection and Neurotoxicity
Current Drug Targets - CNS & Neurological Disorders Current Status of Delivery Systems to Improve Target Efficacy of Oligonu-cleotides
Current Pharmaceutical Design Autologous Formalin-Fixed Tumor Vaccine
Current Pharmaceutical Design Aurora A and B Kinases - Targets of Novel Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Cancer Therapy By Targeting Hypoxia-Inducible Factor-1
Current Cancer Drug Targets Reflecting Back to Bring Nitric Oxide Research to the Laboratory
Current Medicinal Chemistry Molecular Pathways Involved in Apoptotic Cell Death in the Injured Cochlea: Cues to Novel Therapeutic Strategies
Current Pharmaceutical Design Recent Developments in Boron Neutron Capture Therapy (BNCT) Driven by Nanotechnology
Current Chemical Biology