Natural products-prompted chemical biology: phenotypic screening and a new platform for target identification

2016 ◽  
Vol 33 (5) ◽  
pp. 648-654 ◽  
Author(s):  
Hideaki Kakeya
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Chemical Biology ◽  
Target Identification ◽  
Chemical Genetics ◽  
Phenotypic Screening ◽  
Cancer Microenvironment ◽  
Microbial Metabolites ◽  
Cellular Targets ◽  
Target Cancer

This highlight focuses on our recent discoveries and chemical genetics approaches for bioactive microbial metabolites that target cancer cells, the cancer microenvironment, and cell membrane signalling. In addition, the development of two new platforms to identify the cellular targets of these molecules is also discussed.

scholarly journals From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5702
Author(s):  
Quentin T. L. Pasquer ◽  
Ioannis A. Tsakoumagkos ◽  
Sascha Hoogendoorn
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Target Identification ◽  
Biologically Active ◽  
Phenotypic Screening ◽  
Biological Processes ◽  
Chemical Probes ◽  
Target Deconvolution ◽  
Cellular Target ◽  
Screening Approaches

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.

High-Effective Gene Delivery Based on Cyclodextrins Multivalent Assembly in Target Cancer Cells

2022 ◽  
Author(s):  
Yao-Hua Liu ◽  
Yu Liu
Keyword(s):  
Gene Therapy ◽  
Controlled Release ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Cells ◽  
Chemical Biology ◽  
Supramolecular Assembly ◽  
Target Cancer

Nucleic acids condensation and controlled release remain significant challenges of gene therapy in chemical biology and nanotechnology fields. In this work, we have reported a polysaccharide supramolecular assembly constructed by...

scholarly journals Development of a chemogenomics library for phenotypic screening

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bryan Dafniet ◽  
Natacha Cerisier ◽  
Batiste Boezio ◽  
Anaelle Clary ◽  
Pierre Ducrot ◽  
...  
Keyword(s):  
Small Molecules ◽  
Drug Target ◽  
Drug Targets ◽  
Chemical Biology ◽  
Target Identification ◽  
Biological Effects ◽  
Phenotypic Screening ◽  
High Content Imaging ◽  
Advanced Technologies ◽  
System Pharmacology

AbstractWith the development of advanced technologies in cell-based phenotypic screening, phenotypic drug discovery (PDD) strategies have re-emerged as promising approaches in the identification and development of novel and safe drugs. However, phenotypic screening does not rely on knowledge of specific drug targets and needs to be combined with chemical biology approaches to identify therapeutic targets and mechanisms of actions induced by drugs and associated with an observable phenotype. In this study, we developed a system pharmacology network integrating drug-target-pathway-disease relationships as well as morphological profile from an existing high content imaging-based high-throughput phenotypic profiling assay known as “Cell Painting”. Furthermore, from this network, a chemogenomic library of 5000 small molecules that represent a large and diverse panel of drug targets involved in diverse biological effects and diseases has been developed. Such a platform and a chemogenomic library could assist in the target identification and mechanism deconvolution of some phenotypic assays. The usefulness of the platform is illustrated through examples.

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

Study of NSCLC cell migration promoted by NSCLC-Derived Extracellular Vesicle using atomic force microscopy

2021 ◽  
Author(s):  
Shuwei Wang ◽  
Jiajia Wang ◽  
Tuoyu Ju ◽  
Kaige Qu ◽  
Fan Yang ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Cell Migration ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Cancer Microenvironment ◽  
Biological Processes ◽  
Force Microscopy ◽  
Atomic Force ◽  
Cellular Components

Extracellular Vesicles (EVs) secreted by cancer cells have a key role in the cancer microenvironment and progression. Previous studies have mainly focused on molecular functions, cellular components and biological processes...

scholarly journals A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianmin Xiao ◽  
Miao Yan ◽  
Ke Zhou ◽  
Hui Chen ◽  
Zhaowei Xu ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
High Yield ◽  
Ros Generation ◽  
Superoxide Dismutase 1 ◽  
Nuclear Targeting ◽  
Dual Mode ◽  
Red Cell Membrane ◽  
Cancer Cell Death ◽  
Drug Nanocarriers

Abstract The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Phenotypic screening with target identification and validation in the discovery and development of E3 ligase modulators

2021 ◽  
Vol 28 (3) ◽  
pp. 283-299
Author(s):  
Nil Ege ◽  
Habib Bouguenina ◽  
Marianthi Tatari ◽  
Rajesh Chopra
Keyword(s):  
Target Identification ◽  
E3 Ligase ◽  
Phenotypic Screening

scholarly journals Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder Cancer Cells In Vitro

2021 ◽  
pp. 1-17
Author(s):  
Laura E. Griffin ◽  
Sarah E. Kohrt ◽  
Atul Rathore ◽  
Colin D. Kay ◽  
Magdalena M. Grabowska ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Microbial Metabolites ◽  
Bladder Cancer Cells

P57. Manipulating the bone mineral affinity of bisphosphonates to directly target cancer cells in the bone marrow

2008 ◽  
Vol 34 ◽  
pp. 42
Author(s):  
Florence Daubiné ◽  
Pierrick Fournier ◽  
Hal Ebetino ◽  
Philippe Clezardin
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Bone Mineral ◽  
Target Cancer
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