Abstract
Nelfinavir (Viracept®) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS, mostly by cross-reacting with microbial aspartic proteases. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes.
Keywords: Nelfinavir, HIV, protease inhibitor, cancer, endoplasmic reticulum, apoptosis, mitochondria
Current Molecular Pharmacology
Title: New Prospects for Nelfinavir in Non-HIV-Related Diseases
Volume: 3
Author(s): Ansgar Bruning, Andrea Gingelmaier, Klaus Friese and Ioannis Mylonas
Affiliation:
Keywords: Nelfinavir, HIV, protease inhibitor, cancer, endoplasmic reticulum, apoptosis, mitochondria
Abstract: Nelfinavir (Viracept®) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS, mostly by cross-reacting with microbial aspartic proteases. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes.
Export Options
About this article
Cite this article as:
Bruning Ansgar, Gingelmaier Andrea, Friese Klaus and Mylonas Ioannis, New Prospects for Nelfinavir in Non-HIV-Related Diseases, Current Molecular Pharmacology 2010; 3 (2) . https://dx.doi.org/10.2174/1874467211003020091
DOI https://dx.doi.org/10.2174/1874467211003020091 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- 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
-
Editorial (Thematic Issue: Recent Trends in Library Design and Virtual Screening in Medicinal Chemistry and Drug Discovery)
Current Topics in Medicinal Chemistry A Review Exploring Therapeutic Worth of 1,3,4-Oxadiazole Tailored Compounds
Mini-Reviews in Medicinal Chemistry Tolerance Induction by Gene Transfer to Lymphocytes
Current Gene Therapy Pertussis Vaccines: State-of-the-Art and Future Trends
Current Topics in Medicinal Chemistry Targeting Breast Cancer Cells with G4 PAMAM Dendrimers and Valproic Acid Derivative Complexes
Anti-Cancer Agents in Medicinal Chemistry Dendrimers and Dendritic Polymers as Anti-infective Agents: New Antimicrobial Strategies for Therapeutic Drugs
Anti-Infective Agents in Medicinal Chemistry Spices Chemoconstituents as Persuasive Inhibitor of S. typhimurium Virulent Protein L-asparaginase
Letters in Drug Design & Discovery Iron Metabolism: A Promising Target for Antibacterial Strategies
Recent Patents on Anti-Infective Drug Discovery Insights on Antimicrobial Resistance, Biofilms and the Use of Phytochemicals as New Antimicrobial Agents
Current Medicinal Chemistry Synthesis of 3-(7-Methylbenzo[d]oxazol-4-yl) Butanoic Acid: A Precursor of (+)-seco-Pseudopteroxazole and (+)-Pseudopteroxazole
Letters in Organic Chemistry Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms
Current Medicinal Chemistry HIV-1 Infection: Recent Developments in Treatment and Current Management Strategies
Anti-Infective Agents in Medicinal Chemistry Volatilome Metabolomics and Databases, Recent Advances and Needs
Current Metabolomics Biological Activities of Quinoline Derivatives
Mini-Reviews in Medicinal Chemistry Dietary Interventions in Asthma
Current Pharmaceutical Design Synthesis, Characterization, and the Influence of Functionalized Multi-Walled Carbon Nanotubes with Sulfone Derivatives on the Gastric Cancer Cells
Current Nanoscience DD-Ligases as a Potential Target for Antibiotics: Past, Present and Future
Current Medicinal Chemistry In silico Analysis of Toxins of Staphylococcus aureus for Validating Putative Drug Targets
Infectious Disorders - Drug Targets Medicinal Chemistry Perspective of Fused Isoxazole Derivatives
Current Topics in Medicinal Chemistry Enzymes with Phosphotriesterase and Lactonase Activities in Archaea
Current Chemical Biology