Abstract
The mammalian target of rapamycin (mTOR), which assembles into two distinct multiprotein complexes, called mTORC1 and mTORC2, is known as a central regulator of cellular proliferation and maturation. Rictor is one of the key components of mTORC2 and acts as a scaffolding protein to maintain and stabilize mTORC2. Currently, mTORC2 and/or Rictor are increasingly being recognized as attractive targets for novel modalities of anti-cancer therapy. Unfortunately, the safety profile of Rictor- or mTORC2-targeting strategies has been poorly understood due to the lack of an ideal animal model. In the present study, we used zebrafish as an in vivo model system to evaluate the safety of Rictor inhibition. Our data showed that the Rictor of zebrafish was identified to have high sequence homology with mouse Rictor and human Rictor, which validates the rationale of using zebrafish as a research model. Rictor was dispensable in neonatal hematopoiesis and angiogenesis and was not required for vasculogenesis and other organs. These data are consistent with those of previous observations of using tissue-specific Rictor knockout mice model and have potentially important clinical implications. Our findings highlight a good in vivo safety profile for Rictor- or mTORC2-targeting therapy and point to the feasibility and advantages of using the zebrafish model to evaluate the safety of the therapeutic target.
Keywords: Rictor, zebrafish, target, inhibition.
Current Pharmaceutical Design
Title:Evaluation of the in vivo Safety Profiles of Rictor Inhibition Using a Zebrafish Model
Volume: 21 Issue: 12
Author(s): Yang Cao, Lijun Jiang, Lei Zhao, Xiaoxi Zhou, Na Wang, Peilin Zhang, Yuting Tang and Jianfeng Zhou
Affiliation:
Keywords: Rictor, zebrafish, target, inhibition.
Abstract: The mammalian target of rapamycin (mTOR), which assembles into two distinct multiprotein complexes, called mTORC1 and mTORC2, is known as a central regulator of cellular proliferation and maturation. Rictor is one of the key components of mTORC2 and acts as a scaffolding protein to maintain and stabilize mTORC2. Currently, mTORC2 and/or Rictor are increasingly being recognized as attractive targets for novel modalities of anti-cancer therapy. Unfortunately, the safety profile of Rictor- or mTORC2-targeting strategies has been poorly understood due to the lack of an ideal animal model. In the present study, we used zebrafish as an in vivo model system to evaluate the safety of Rictor inhibition. Our data showed that the Rictor of zebrafish was identified to have high sequence homology with mouse Rictor and human Rictor, which validates the rationale of using zebrafish as a research model. Rictor was dispensable in neonatal hematopoiesis and angiogenesis and was not required for vasculogenesis and other organs. These data are consistent with those of previous observations of using tissue-specific Rictor knockout mice model and have potentially important clinical implications. Our findings highlight a good in vivo safety profile for Rictor- or mTORC2-targeting therapy and point to the feasibility and advantages of using the zebrafish model to evaluate the safety of the therapeutic target.
Export Options
About this article
Cite this article as:
Cao Yang, Jiang Lijun, Zhao Lei, Zhou Xiaoxi, Wang Na, Zhang Peilin, Tang Yuting and Zhou Jianfeng, Evaluation of the in vivo Safety Profiles of Rictor Inhibition Using a Zebrafish Model, Current Pharmaceutical Design 2015; 21 (12) . https://dx.doi.org/10.2174/1381612821666150105120955
DOI https://dx.doi.org/10.2174/1381612821666150105120955 |
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
-
The Therapeutic Potential of Toll-Like Receptor 7 Stimulation in Asthma
Inflammation & Allergy - Drug Targets (Discontinued) Circulating MicroRNAs as Potential Biomarkers in Glioma: A Mini-Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Smad-Signaling in Mammary Gland Development and Tumorigenesis
Current Signal Transduction Therapy Neuroblastoma and Stem Cell Therapy: An Updated Review
CNS & Neurological Disorders - Drug Targets Targeting Telomerase for Cancer Therapy
Current Cancer Therapy Reviews Erlotinib in Glioblastoma - Lost in Translation?
Anti-Cancer Agents in Medicinal Chemistry Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design Exosomes Harnessed as Nanocarriers for Cancer Therapy - Current Status and Potential for Future Clinical Applications
Current Molecular Medicine Role of Nuclear Steroid Receptors in Apoptosis
Current Medicinal Chemistry MicroRNAs: Key Players in Microglia and Astrocyte Mediated Inflammation in CNS Pathologies
Current Medicinal Chemistry Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases
Current Protein & Peptide Science The Application of Stimuli-responsive Nanocarriers for Targeted Drug Delivery
Current Topics in Medicinal Chemistry In Vivo Monitoring of Cell Based Therapy in the Liver
Current Molecular Imaging (Discontinued) Thyroid Hormones Crosstalk with Growth Factors: Old Facts and New Hypotheses
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review
Current Medicinal Chemistry Inhibition of HIV-1 Replication by RNA-Based Strategies
Current HIV Research A Role of Immunotherapy in Metastatic Malignant Melanoma
Central Nervous System Agents in Medicinal Chemistry Imidazoquinolines: Recent Developments in Anticancer Activity
Mini-Reviews in Medicinal Chemistry In Vitro Synergistic Interaction between DTA0100 and Radiation in Human Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry