Abstract
The ability of certain DNA sequences to form G-quartet structures has been exploited recently to develop novel anti-cancer agents including small molecules that promote G-quartet formation within the c-MYC promoter thereby repressing c-MYC transcription and introducing G-quartet-forming oligodeoxynucleotides (GQ-ODN) into cancer cells resulting in p53-dependent cell cycle arrest and inhibition of DNA replication. GQ-ODNs also have been developed as potent inhibitors of signal transducer and activator of transcription (STAT) 3, a critical mediator of oncogenic signaling in many cancers. This review summarizes the rational design of G-quartet forming DNA drugs as Stat3 inhibitors. Topics that are reviewed include the strategy of structure-based drug design, establishment of a structure-activity relationship, development of a novel intracellular delivery system for G-quartet-forming DNA agents and in vivo drug testing to assess the anti-cancer effects of DNA drugs in tumor xenografts. Results to date with GQ-ODN targeting Stat3 are encouraging, and it is hoped that continued pursuit of the methodology outlined here may lead to development of an effective agent for treatment of metastatic cancers, such as prostate and breast, in which Stat3 is constitutively activated.
Keywords: dna drugs, g-quartet oligodeoxynucleotides (gq-odn), signal transducer and activator of transcription (stat) 3, apoptosis, cancer therapy, prostate cancer, breast cancer, drug delivery, drug design
Current Pharmaceutical Design
Title: Rational Drug Design of G-Quartet DNA as Anti-Cancer Agents
Volume: 11 Issue: 22
Author(s): N. Jing, W. Sha, Y. Li, W. Xiong and D. J. Tweardy
Affiliation:
Keywords: dna drugs, g-quartet oligodeoxynucleotides (gq-odn), signal transducer and activator of transcription (stat) 3, apoptosis, cancer therapy, prostate cancer, breast cancer, drug delivery, drug design
Abstract: The ability of certain DNA sequences to form G-quartet structures has been exploited recently to develop novel anti-cancer agents including small molecules that promote G-quartet formation within the c-MYC promoter thereby repressing c-MYC transcription and introducing G-quartet-forming oligodeoxynucleotides (GQ-ODN) into cancer cells resulting in p53-dependent cell cycle arrest and inhibition of DNA replication. GQ-ODNs also have been developed as potent inhibitors of signal transducer and activator of transcription (STAT) 3, a critical mediator of oncogenic signaling in many cancers. This review summarizes the rational design of G-quartet forming DNA drugs as Stat3 inhibitors. Topics that are reviewed include the strategy of structure-based drug design, establishment of a structure-activity relationship, development of a novel intracellular delivery system for G-quartet-forming DNA agents and in vivo drug testing to assess the anti-cancer effects of DNA drugs in tumor xenografts. Results to date with GQ-ODN targeting Stat3 are encouraging, and it is hoped that continued pursuit of the methodology outlined here may lead to development of an effective agent for treatment of metastatic cancers, such as prostate and breast, in which Stat3 is constitutively activated.
Export Options
About this article
Cite this article as:
Jing N., Sha W., Li Y., Xiong W. and Tweardy J. D., Rational Drug Design of G-Quartet DNA as Anti-Cancer Agents, Current Pharmaceutical Design 2005; 11 (22) . https://dx.doi.org/10.2174/1381612054546761
DOI https://dx.doi.org/10.2174/1381612054546761 |
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
-
High Therapeutic Potential for Systemic Delivery of a Liposomeconjugated Herpes Simplex Virus
Current Cancer Drug Targets Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Smad-Signaling in Mammary Gland Development and Tumorigenesis
Current Signal Transduction Therapy Expression and Function of Angiomodulating Cytokines in Rheumatoid Arthritis and Experimental Arthritis: Important Therapeutic Targets
Current Immunology Reviews (Discontinued) Radiogenetic Therapy: Strategies to Overcome Tumor Resistance
Current Pharmaceutical Design Eliminating Ovarian Cancer Stem Cells: A Potential Therapeutic Target for Ovarian Cancer Chemoresistance
Current Protein & Peptide Science Meet Our Co-Editor
Current Signal Transduction Therapy Improving the Hsp90 Inhibitors Containing 4-(2,4-Dihydroxyphenyl)-1,2,3-thiadiazole Scaffold: Synthesis, Affinity and Effect on Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Antiangiogenic Gene Therapy in Cancer
Current Genomics Application of Metabolomics in Drug Discovery, Development and Theranostics
Current Metabolomics Bioconjugation of Ionophore Antibiotics: A Way to Obtain Hybrids with Potent Biological Activity
Mini-Reviews in Organic Chemistry Selectively Replicating Adenoviruses for Oncolytic Therapy
Current Cancer Drug Targets Structure, Function and Inhibition of Bcl-2 Family Proteins: A New Target for Anti-Tumor Agents
Mini-Reviews in Medicinal Chemistry Fluoride Effects: The Two Faces of Janus
Current Medicinal Chemistry Role of Unani Medicines in Cancer Control and Management
Current Drug Therapy The Role of PET/CT and SPECT/CT in Oncology Drug Development
Current Molecular Imaging (Discontinued) Molecular Mechanism of Anti-tumor Effect by Triptolide in Hematological Malignancies
Current Signal Transduction Therapy Crossed Cerebellar Diaschisis in Alzheimer’s Disease
Current Alzheimer Research CB1 Cannabinoid Receptors and their Associated Proteins
Current Medicinal Chemistry Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease
Current Alzheimer Research