Abstract
Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these compounds like those targeted to entry and mitotic kinases, mitotic kinesins/motor proteins, and multiprotein complexes have been evaluated in vitro and in animal models, and some of them have reached clinical trials. Despite promising preclinical results, in many cases, the efficacy demonstrated by these new antimitotics was not better than current microtubule inhibitors. In this paper we review present and future strategies on the search for new antimitotic compounds based on identification of new protein targets and development of multifunctional inhibitors of mitosis in cancer cells.
Keywords: Cancer, drug development, kinase, kinesin, mitosis, multiprotein complexes.
Current Topics in Medicinal Chemistry
Title:Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents
Volume: 14 Issue: 20
Author(s): S. Novio, M. Freire-Garabal and M.J. Núnez
Affiliation:
Keywords: Cancer, drug development, kinase, kinesin, mitosis, multiprotein complexes.
Abstract: Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these compounds like those targeted to entry and mitotic kinases, mitotic kinesins/motor proteins, and multiprotein complexes have been evaluated in vitro and in animal models, and some of them have reached clinical trials. Despite promising preclinical results, in many cases, the efficacy demonstrated by these new antimitotics was not better than current microtubule inhibitors. In this paper we review present and future strategies on the search for new antimitotic compounds based on identification of new protein targets and development of multifunctional inhibitors of mitosis in cancer cells.
Export Options
About this article
Cite this article as:
Novio S., Freire-Garabal M. and Núnez M.J., Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents, Current Topics in Medicinal Chemistry 2014; 14 (20) . https://dx.doi.org/10.2174/1568026614666141130093425
DOI https://dx.doi.org/10.2174/1568026614666141130093425 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...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
-
KIAA0101 in Malignant Pleural Mesothelioma: A Potential Diagnostic
and Prognostic Marker
Combinatorial Chemistry & High Throughput Screening Separation of Ginseng Active Ingredients and their Roles in Cancer Metastasis Supplementary Therapy
Current Drug Metabolism What they are, How they Work and Why they do What they do? The Story of SV40-derived Gene Therapy Vectors and What They Have to Offer
Current Gene Therapy Nanomedicine to Overcome Cancer Multidrug Resistance
Current Drug Metabolism Automated Brain Tumour Detection and Classification using Deep Features and Bayesian Optimised Classifiers
Current Medical Imaging Targeting Mutant-p53 for Cancer Treatment: Are We There Yet?
Current Molecular Pharmacology Curcumin: Not So Spicy After All
Mini-Reviews in Medicinal Chemistry The Role of CXCR3 in Neurological Diseases
Current Neuropharmacology Jumping on the Train of Personalized Medicine: A Primer for Non- Geneticist Clinicians: Part 3. Clinical Applications in the Personalized Medicine Area
Current Psychiatry Reviews Patent Selections
Recent Patents on Biomarkers Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer
Current Drug Targets TGFß, a Potent Regulator of Tumor Microenvironment and Host Immune Response, Implication for Therapy
Current Molecular Medicine Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma <i>via Akt</i> Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry CIAPIN1 siRNA Inhibits Proliferation, Migration and Promotes Apoptosis of VSMCs by Regulating Bcl-2 and Bax
Current Neurovascular Research Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases
Current Topics in Medicinal Chemistry Novel Anticancer Strategy Aimed at Targeting Shelterin Complexes by the Induction of Structural Changes in Telomeric DNA: Hitting two Birds with one Stone
Current Cancer Drug Targets The Neurotrophic and Antiangiogenic Functions of PEDF: A Reflection of its Variable Phosphorylation States
Current Genomics Neuropeptide-Derived Antimicrobial Peptides from Invertebrates for Biomedical Applications
Current Medicinal Chemistry Gankyrin Oncoprotein: Structure, Function, and Involvement in Cancer
Current Chemical Biology Polymer-Based Drug Delivery Systems, Development and Pre-Clinical Status
Current Pharmaceutical Design