Abstract
Retinoic acid and derivatives (retinoids) exert their anti-neoplastic action through three different, though partially overlapping mechanisms: growth-inhibition, cyto-differentiation and apoptosis. Retinoid related molecules (RRMs) are a promising class of synthetic retinoic acid derivatives endowed with selective apoptotic activity on a large variety of leukemic and solid tumor cells. The in vitro apoptotic activity of RRMs translates into in vivo efficacy in a number of experimental models of neoplasia. The prototype of this novel family of cytotoxic agents is CD437, a conformation restricted retinoid originally developed as a selective RARγ agonist. A number of new RRM congeners, including ST1926, MM002, MM11453 and MX-3350-1, have been recently reported in the literature. Some of these compounds have a stronger apoptotic potential, a lower level of toxicity and a better pharmacokinetic profile than CD437. RRMs have a molecular mechanism of action that is entirely different from that of many other known chemotherapeutics. These compounds induce apoptosis in retinoic acid- and multi-drug-resistant neoplastic cells. The apoptotic process triggered by RRMs is independent of p53 activation and proceeds through a novel pathway in which the mitochondrion seems to play a pivotal role. RRMs show only very limited cross-resistance with other classes of chemotherapeutic agents and show synergistic interactions with a number of classical cyto-toxic agents. The article presents a critical overview of the current knowledge on the pharmacology of RRMs focussing on such issues as the spectrum of cytotoxic activity, the molecular mechanisms of action and the pre-clinical basis of clinical development.
Keywords: Retinoid, Apoptotic Agents, mitochondrion, chemotherapeutic, CD437, Oncology
Current Pharmaceutical Design
Title: Retinoid Related Molecules an Emerging Class of Apoptotic Agents with Promising Therapeutic Potential in Oncology: Pharmacological Activity and Mechanisms of Action
Volume: 10 Issue: 4
Author(s): Enrico Garattini, Maurizio Gianni and Mineko Terao
Affiliation:
Keywords: Retinoid, Apoptotic Agents, mitochondrion, chemotherapeutic, CD437, Oncology
Abstract: Retinoic acid and derivatives (retinoids) exert their anti-neoplastic action through three different, though partially overlapping mechanisms: growth-inhibition, cyto-differentiation and apoptosis. Retinoid related molecules (RRMs) are a promising class of synthetic retinoic acid derivatives endowed with selective apoptotic activity on a large variety of leukemic and solid tumor cells. The in vitro apoptotic activity of RRMs translates into in vivo efficacy in a number of experimental models of neoplasia. The prototype of this novel family of cytotoxic agents is CD437, a conformation restricted retinoid originally developed as a selective RARγ agonist. A number of new RRM congeners, including ST1926, MM002, MM11453 and MX-3350-1, have been recently reported in the literature. Some of these compounds have a stronger apoptotic potential, a lower level of toxicity and a better pharmacokinetic profile than CD437. RRMs have a molecular mechanism of action that is entirely different from that of many other known chemotherapeutics. These compounds induce apoptosis in retinoic acid- and multi-drug-resistant neoplastic cells. The apoptotic process triggered by RRMs is independent of p53 activation and proceeds through a novel pathway in which the mitochondrion seems to play a pivotal role. RRMs show only very limited cross-resistance with other classes of chemotherapeutic agents and show synergistic interactions with a number of classical cyto-toxic agents. The article presents a critical overview of the current knowledge on the pharmacology of RRMs focussing on such issues as the spectrum of cytotoxic activity, the molecular mechanisms of action and the pre-clinical basis of clinical development.
Export Options
About this article
Cite this article as:
Garattini Enrico, Gianni Maurizio and Terao Mineko, Retinoid Related Molecules an Emerging Class of Apoptotic Agents with Promising Therapeutic Potential in Oncology: Pharmacological Activity and Mechanisms of Action, Current Pharmaceutical Design 2004; 10 (4) . https://dx.doi.org/10.2174/1381612043453351
DOI https://dx.doi.org/10.2174/1381612043453351 |
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
-
Engineered Liposomes for Drug Delivery and Biomedical Imaging
Recent Patents on Nanomedicine Ex Vivo Gene Therapy and Vision
Current Gene Therapy Glial Reaction in Parkinsons Diseases: Inflammatory Activation Signaling of Glia as a Potential Therapeutic Target
Current Signal Transduction Therapy Hijacking the Hedgehog Pathway in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Melatonin and Melatoninergic Drugs as Therapeutic Agents: Ramelteon and Agomelatine, the Two Most Promising Melatonin Receptor Agonists
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Meet the Editorial Board:
Current Alzheimer Research Pleiotrophin as a Possible New Target for Angiogenesis-Related Diseases and Cancer
Recent Patents on Anti-Cancer Drug Discovery Regulation of Hypoxia-inducible Factor-1α and Vascular Endothelial Growth Factor Signaling by Plant Flavonoids
Mini-Reviews in Medicinal Chemistry Nanoscale Formulations and Diagnostics With Their Recent Trends: A Major Focus of Future Nanotechnology
Current Pharmaceutical Design Tubulin Inhibitors: A Patent Survey
Recent Patents on Anti-Cancer Drug Discovery A Review of the ADAMTS Family, Pharmaceutical Targets of the Future
Current Pharmaceutical Design Inhibition of Polo-Like Kinase 1 by BI2536 Reverses the Multidrug Resistance of Human Hepatoma Cells In Vitro and In Vivo
Anti-Cancer Agents in Medicinal Chemistry Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Recent Patents and Patent Applications Relating to mTOR Pathway
Recent Patents on DNA & Gene Sequences <i>Lophira alata</i> Suppresses Phorbol Ester-Mediated Increase in Cell Growth via Inhibition of Protein Kinase C-α/Akt in Glioblastoma Cells
Anti-Cancer Agents in Medicinal Chemistry Targeted Delivery of Tumor Suppressor microRNA-1 by Transferrin- Conjugated Lipopolyplex Nanoparticles to Patient-Derived Glioblastoma Stem Cells
Current Pharmaceutical Biotechnology Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection
Current Molecular Pharmacology In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber:Implication for Anti-Cancer Drugs Targeting Secretome
Recent Patents on Anti-Cancer Drug Discovery Upregulation of Cytoskeleton Protein and Extracellular Matrix Protein Induced by Stromal-Derived Nitric Oxide Promotes Lung Cancer Invasion and Metastasis
Current Molecular Medicine Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor Therapy
Current Drug Targets