Abstract
In recent years, a series of new and highly cytotoxic analogues of CC-1065 and the duocarmycins have been developed that can be transformed into much less toxic prodrugs for the use in antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) and prodrug monotherapy (PMT) of cancer. In all these approaches, a relatively non-toxic prodrug is applied and subsequently converted selectively in the tumour tissue into a highly cytotoxic drug, thus reducing undesired side effects accompanying conventional chemotherapy. Here, the design and biological evaluation of prodrugs based on analogues of CC-1065 and the duocarmycins for the use in tumour selective cancer therapies is reviewed. The advantage of this approach is the excellent therapeutic index of some of the new prodrugs of over 5000 and the high cytotoxicity of the corresponding drugs with IC50 values of as low as 16 pM (IC50: concentration required for 50 % growth inhibition of target cells). In addition, a novel method for the correlation of the alkylation efficiency and the cytotoxicity based on mass spectrometry is described.
Keywords: ADEPT, anti-tumour agents, CC-1065, duocarmycins, targeted cancer therapy, PMT, prodrugs
Anti-Cancer Agents in Medicinal Chemistry
Title: Novel Analogues of CC-1065 and the Duocarmycins for the Use in Targeted Tumour Therapies
Volume: 9 Issue: 3
Author(s): Lutz F. Tietze and Birgit Krewer
Affiliation:
Keywords: ADEPT, anti-tumour agents, CC-1065, duocarmycins, targeted cancer therapy, PMT, prodrugs
Abstract: In recent years, a series of new and highly cytotoxic analogues of CC-1065 and the duocarmycins have been developed that can be transformed into much less toxic prodrugs for the use in antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) and prodrug monotherapy (PMT) of cancer. In all these approaches, a relatively non-toxic prodrug is applied and subsequently converted selectively in the tumour tissue into a highly cytotoxic drug, thus reducing undesired side effects accompanying conventional chemotherapy. Here, the design and biological evaluation of prodrugs based on analogues of CC-1065 and the duocarmycins for the use in tumour selective cancer therapies is reviewed. The advantage of this approach is the excellent therapeutic index of some of the new prodrugs of over 5000 and the high cytotoxicity of the corresponding drugs with IC50 values of as low as 16 pM (IC50: concentration required for 50 % growth inhibition of target cells). In addition, a novel method for the correlation of the alkylation efficiency and the cytotoxicity based on mass spectrometry is described.
Export Options
About this article
Cite this article as:
Tietze F. Lutz and Krewer Birgit, Novel Analogues of CC-1065 and the Duocarmycins for the Use in Targeted Tumour Therapies, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (3) . https://dx.doi.org/10.2174/1871520610909030304
DOI https://dx.doi.org/10.2174/1871520610909030304 |
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
-
Wnt/β-Catenin/LEF-1 Signaling in Chronic Lymphocytic Leukemia (CLL): A Target for Current and Potential Therapeutic Options
Current Cancer Drug Targets The use of nanocarriers in acute myeloid leukaemia therapy: challenges and current status.
Current Pharmaceutical Biotechnology Management of Early Stage Chronic Myeloid Leukemia: State-of-the-art Approach and Future Perspectives
Current Cancer Drug Targets Cellular and Molecular Networks in Chronic Myeloid Leukemia: The Leukemic Stem, Progenitor and Stromal Cell Interplay
Current Drug Targets Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents Evaluating Treatment Response of Chronic Myeloid Leukemia: Emerging Science and Technology
Current Cancer Drug Targets Limiting Functional Deficiency Following Stroke: Exploiting Different Stem Cell Reservoirs
Current Neuropharmacology Therapeutic Potential of Photochemically Active Metal Complexes based on Interaction with Enzymes
Current Topics in Medicinal Chemistry Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway
Current Neurovascular Research Posterior Reversible Encephalopathy Syndrome in Leukemic Children: A Sensitive Issue
Current Drug Safety Nucleoside Transporter Proteins
Current Vascular Pharmacology Editorial (Hot Topics: Naturally Occurring Molecules and Anticancer Combination Therapies in the Era of Personalized Medicine and Economic Crisis)
Current Pharmaceutical Design Inhibitors of the PI3K/Akt/mTOR Pathway: New Hope for Breast Cancer Patients
Recent Patents on Anti-Cancer Drug Discovery Gender Disparity in Pediatric Diseases
Current Molecular Medicine Copanlisib: Novel PI3K Inhibitor for the Treatment of Lymphoma
Anti-Cancer Agents in Medicinal Chemistry Isatoic Anhydride: A Fascinating and Basic Molecule for the Synthesis of Substituted Quinazolinones and Benzo di/triazepines
Current Organic Chemistry Ceramidases in Hematological Malignancies: Senseless or Neglected Target?
Anti-Cancer Agents in Medicinal Chemistry Do Not Say Ever Never More: The Ins and Outs of Antiangiogenic Therapies
Current Pharmaceutical Design Targeting Regulatory T Cells for Anticancer Therapy
Mini-Reviews in Medicinal Chemistry Therapeutic Perspectives for cN-II in Cancer.
Current Medicinal Chemistry