Abstract
Antibody-drug conjugates (ADCs) are an emerging area of study within medicinal chemistry and are thought of as sophisticated drug delivery systems due to their specificity to a disease-targeted antigen. ADCs have been actively utilized as therapeutics for hematological and solid tumor cancers due to their capability to deliver a cytotoxic compound to a specific cancer cell without affecting normal cells. An antibody drug conjugate has three major constituents: a monoclonal antibody (mAb), a chemical linker, and a potent cytotoxic payload. There has been a continuing effort to optimize antibody-drug conjugates, with the primary focus of design and development directed at either the mAb or the chemical linker, with little effort devoted to the optimization of payload compounds. In fact, among the 114 ongoing or recently completed clinical trials, there is generally a lack of diversity in the cytotoxic payloads that are utilized, with only seven payload compounds reported (four additional trials are ongoing with structures that have not been reported). Six of these seven payload compounds are derived from natural product sources, highlighting the importance of natural products as cytotoxic payloads for ADC.
Keywords: Antibody drug conjugate (ADC), Cytotoxic payload, Natural products.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates
Volume: 14 Issue: 24
Author(s): Samantha M. Gromek and Marcy J. Balunas
Affiliation:
Keywords: Antibody drug conjugate (ADC), Cytotoxic payload, Natural products.
Abstract: Antibody-drug conjugates (ADCs) are an emerging area of study within medicinal chemistry and are thought of as sophisticated drug delivery systems due to their specificity to a disease-targeted antigen. ADCs have been actively utilized as therapeutics for hematological and solid tumor cancers due to their capability to deliver a cytotoxic compound to a specific cancer cell without affecting normal cells. An antibody drug conjugate has three major constituents: a monoclonal antibody (mAb), a chemical linker, and a potent cytotoxic payload. There has been a continuing effort to optimize antibody-drug conjugates, with the primary focus of design and development directed at either the mAb or the chemical linker, with little effort devoted to the optimization of payload compounds. In fact, among the 114 ongoing or recently completed clinical trials, there is generally a lack of diversity in the cytotoxic payloads that are utilized, with only seven payload compounds reported (four additional trials are ongoing with structures that have not been reported). Six of these seven payload compounds are derived from natural product sources, highlighting the importance of natural products as cytotoxic payloads for ADC.
Export Options
About this article
Cite this article as:
Gromek M. Samantha and Balunas J. Marcy, Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates, Current Topics in Medicinal Chemistry 2014; 14 (24) . https://dx.doi.org/10.2174/1568026615666141208111253
DOI https://dx.doi.org/10.2174/1568026615666141208111253 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
The Radiosensitizing Effect of Olanzapine as an Antipsychotic Medication
on Glioblastoma Cell
Current Radiopharmaceuticals Is VEGF a Key Target of Cotinine and Other Potential Therapies Against Alzheimer Disease?
Current Alzheimer Research State-of-the-Art Magnetic Resonance Spectroscopy in Oncologic Imaging
Current Molecular Imaging (Discontinued) Vasoactive Factors and Diabetic Retinopathy: Vascular Endothelial Growth Factor, Cycoloxygenase-2 and Nitric Oxide
Current Pharmaceutical Design Determination of Dysregulated miRNA Expression Levels by qRT-PCR after the Application of Usnic Acid to Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Antibody-Onconase Conjugates: Cytotoxicity and Intracellular Routing
Current Pharmaceutical Biotechnology Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update
Current Medicinal Chemistry Synthesis and Broad Spectrum Antibacterial Activity of Magnetite Ferrofluid
Current Nanoscience Systems Biology Approach for the Identification of Diagnostic and Therapeutic Targets in Medulloblastomas
Current Pharmacogenomics and Personalized Medicine Clinical Experiment of Mutant Herpes Simplex Virus HF10 Therapy for Cancer
Current Cancer Drug Targets Pharmacotherpy and Alzheimer’s Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach
Current Pharmaceutical Design What Makes Y Family Pols Potential Candidates for Molecular Targeted Therapies and Novel Biotechnological Applications
Current Molecular Medicine Copper Complexes as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry cAMP-Mediated Regulation of CYP Enzymes and Its Application in Chemotherapy
Drug Metabolism Letters Identification of Biomarkers and Functional Modules from Genomic Data in Stage-wise Breast Cancer
Current Bioinformatics The Role of Ghrelin Signals in Breast Cancer- A Systematic Review
Current Signal Transduction Therapy Neuroinflammation: A Therapeutic Target of Cotinine for the Treatment of Psychiatric Disorders?
Current Pharmaceutical Design The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued) Crude Venom from Nematocysts of the Jellyfish Pelagia noctiluca as a Tool to Study Cell Physiology
Central Nervous System Agents in Medicinal Chemistry P53 Mdm2 Inhibitors
Current Pharmaceutical Design