Abstract
Aims: Total twenty-nine [1,2,4]triazolo[4,3-a]pyrazine derivatives were designed and synthesized.
Method: The target compounds, especially 4aa, showed potent activity to inhibit c-Met both in an enzyme assay and a cellular assay. The comprehensive screening for the inhibition of 60 different kinases revealed that 4aa could selectively inhibit c-Met while had no effect on other kinases, indicating 4aa is an excellent c-Met selective inhibitor. Result: The flow cytometry studies found that 4aa had a similar behavior to the positive control SGX-523 in terms of causing the tumor cell apoptosis and blocking cell-cycle progression. More importantly, 4aa showed much better pharmacokinetic properties than SGX-523. Altogether, the findings suggested the target compounds may be potential anti-tumor drug candidates.Keywords: Antitumor, c-Met inhibitors, selectivity, pharmacokinetic properties, [1, 2, 4] Triazol [4, 3-a] pyridine derivatives, apoptosis.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties
Volume: 17 Issue: 8
Author(s): Junjun Zhao, Shaohua Gou*, Xiaobing Zhang, Yan Liang and Lei Fang*
Affiliation:
- Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189,China
- Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189,China
Keywords: Antitumor, c-Met inhibitors, selectivity, pharmacokinetic properties, [1, 2, 4] Triazol [4, 3-a] pyridine derivatives, apoptosis.
Abstract: Aims: Total twenty-nine [1,2,4]triazolo[4,3-a]pyrazine derivatives were designed and synthesized.
Method: The target compounds, especially 4aa, showed potent activity to inhibit c-Met both in an enzyme assay and a cellular assay. The comprehensive screening for the inhibition of 60 different kinases revealed that 4aa could selectively inhibit c-Met while had no effect on other kinases, indicating 4aa is an excellent c-Met selective inhibitor. Result: The flow cytometry studies found that 4aa had a similar behavior to the positive control SGX-523 in terms of causing the tumor cell apoptosis and blocking cell-cycle progression. More importantly, 4aa showed much better pharmacokinetic properties than SGX-523. Altogether, the findings suggested the target compounds may be potential anti-tumor drug candidates.Export Options
About this article
Cite this article as:
Zhao Junjun, Gou Shaohua*, Zhang Xiaobing, Liang Yan and Fang Lei*, Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1871520616666161031142619
DOI https://dx.doi.org/10.2174/1871520616666161031142619 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
-
Significance of P2X7 Receptor Variants to Human Health and Disease
Recent Patents on DNA & Gene Sequences Advances in the Development of Class I Phosphoinositide 3-Kinase (PI3K) Inhibitors
Current Topics in Medicinal Chemistry Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions
Recent Patents on Anti-Cancer Drug Discovery Autologous Formalin-Fixed Tumor Vaccine
Current Pharmaceutical Design Endogenous Retroelements in Cellular Senescence and Related Pathogenic Processes: Promising Drug Targets in Age-Related Diseases
Current Drug Targets Functional Nanoplatforms for Enhancement of Chemotherapeutic Index
Anti-Cancer Agents in Medicinal Chemistry Bergenin - A Biologically Active Scaffold: Nanotechnological Perspectives
Current Topics in Medicinal Chemistry Serum Procalcitonin Levels in Febrile Patients with Systemic Autoimmune Diseases
Current Rheumatology Reviews Solvent-Free and Self-Catalyzed Three-Component Synthesis of Diversely Substituted Pyrazolo[1,4]thiazepinones of Potential Antitumor Activity
Current Organic Synthesis Bee Venom: Its Potential Use in Alternative Medicine
Anti-Infective Agents Developments in the Application of 1,2,3-Triazoles in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy
Current Drug Targets Radiopharmaceuticals to In Vivo Characterize Adrenal Incidentalomas:The Integrated Role of Radionuclide and Radiological Techniques
Current Radiopharmaceuticals Angiogenesis as a therapeutic target in breast cancer
Mini-Reviews in Medicinal Chemistry The VHL Tumor Suppressor: Master Regulator of HIF
Current Pharmaceutical Design Estrogen Receptor Beta (ERβ) Expression in Different Subtypes of Malignant Pleural Mesothelioma
Current Respiratory Medicine Reviews Matrix Metalloproteinases: New Routes to the Use of MT1-MMP As A Therapeutic Target in Angiogenesis-Related Disease
Current Pharmaceutical Design Embryonic Stem Cell-Derived Hematopoietic Stem Cells: Challenges in Development, Differentiation, and Immunogenicity
Current Topics in Medicinal Chemistry Anti-Inflammatory Iridoids of Botanical Origin
Current Medicinal Chemistry