scholarly journals High throughput screening of natural products for LDH inhibition as an anti‐mitotic therapeutic target (585.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Shihab Deiab ◽  
Elizabeth Mazzio ◽  
Najla Zarmouh ◽  
Nzinga Mack ◽  
Karam Soliman
Keyword(s):  
Natural Products ◽  
High Throughput ◽  
Therapeutic Target ◽  
High Throughput Screening

scholarly journals Multiplex Enzyme Assays and Inhibitor Screening by Mass Spectrometry

2010 ◽  
Vol 15 (8) ◽  
pp. 1001-1007 ◽  
Author(s):  
Rakesh Rathore ◽  
Patrick Pribil ◽  
Jay J. Corr ◽  
William L. Seibel ◽  
Artem Evdokimov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Therapeutic Target ◽  
High Throughput Screening ◽  
Multiplex Assay ◽  
Enzyme Assays ◽  
Readout System ◽  
Inhibitor Screening ◽  
Serial Process ◽  
Pass Through

Current methods for high-throughput screening (HTS) use a serial process to evaluate compounds as inhibitors toward a single therapeutic target, but as the demand to reduce screening time and cost continues to grow, one solution is the development of multiplex technology. In this communication, the multiplex assay capability of a mass spectrometry (MS)–based readout system is verified using a kinase and esterase reaction simultaneously. Furthermore, the MS-based readout is shown to be compatible with a typical HTS workflow by identifying and validating several new inhibitors for each enzyme from a small library of compounds. These data confirm that it is possible to monitor inhibition of multiple therapeutic targets with one pass through the compound repository, thus demonstrating the potential for MS-based methods to become a method of choice for HTS of isolated enzymes.

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

scholarly journals A High Throughput Screening Platform for Skin Tuning Properties from Natural Products: Identification of Skin Tanning Compounds

2016 ◽  
Vol 06 (05) ◽  
pp. 199-209 ◽  
Author(s):  
Gallant K. L. Chan ◽  
Kevin Q. Wu ◽  
Zack C. F. Wong ◽  
Aster H. Y. Fung ◽  
Xuyan Lin ◽  
...  
Keyword(s):  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
Screening Platform ◽  
Skin Tanning

scholarly journals A Gene Expression High-Throughput Screen (GE-HTS) for Coordinated Detection of Functionally Similar Effectors in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3143
Author(s):  
Chaitra Rao ◽  
Dianna H. Huisman ◽  
Heidi M. Vieira ◽  
Danielle E. Frodyma ◽  
Beth K. Neilsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
Loss Of Function ◽  
Synthetic Lethal ◽  
Genome Wide ◽  
Pathway Activation ◽  
Kinase Suppressor Of Ras ◽  
Kinase Cascade

Genome-wide, loss-of-function screening can be used to identify novel vulnerabilities upon which specific tumor cells depend for survival. Functional Signature Ontology (FUSION) is a gene expression-based high-throughput screening (GE-HTS) method that allows researchers to identify functionally similar proteins, small molecules, and microRNA mimics, revealing novel therapeutic targets. FUSION uses cell-based high-throughput screening and computational analysis to match gene expression signatures produced by natural products to those produced by small interfering RNA (siRNA) and synthetic microRNA libraries to identify putative protein targets and mechanisms of action (MoA) for several previously undescribed natural products. We have used FUSION to screen for functional analogues to Kinase suppressor of Ras 1 (KSR1), a scaffold protein downstream of Ras in the Raf-MEK-ERK kinase cascade, and biologically validated several proteins with functional similarity to KSR1. FUSION incorporates bioinformatics analysis that may offer higher resolution of the endpoint readout than other screens which utilize Boolean outputs regarding a single pathway activation (i.e., synthetic lethal and cell proliferation). Challenges associated with FUSION and other high-content genome-wide screens include variation, batch effects, and controlling for potential off-target effects. In this review, we discuss the efficacy of FUSION to identify novel inhibitors and oncogene-induced changes that may be cancer cell-specific as well as several potential pitfalls within FUSION and best practices to avoid them.

scholarly journals Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3714
Author(s):  
G. Lavender Hackman ◽  
Meghan Collins ◽  
Xiyuan Lu ◽  
Alessia Lodi ◽  
John DiGiovanni ◽  
...  
Keyword(s):  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Cancer Drugs ◽  
Antagonistic Effects

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.

High-Throughput Screening of Chemical Libraries for Modulators of Gene Promoter Activity ofHLA-B2705: Environmental Pathogenesis and Therapeutics of Ankylosing Spondylitis

2011 ◽  
Vol 38 (6) ◽  
pp. 1061-1065 ◽  
Author(s):  
LIKE ZHAO ◽  
CHIN-HSIU LIU ◽  
DAVID YU
Keyword(s):  
Natural Products ◽  
Ankylosing Spondylitis ◽  
High Throughput ◽  
High Throughput Screening ◽  
Promoter Activity ◽  
Fruits And Vegetables ◽  
Gene Promoter ◽  
Culture Conditions ◽  
Hla B27 ◽  
New Research

Objective.Ankylosing spondylitis (AS) is a highly heritable disease withHLA-B27being the strongest susceptible gene. In order to survey the environmental triggers for arthritis development, we used a high-throughput technique to screen the effects of 12,264 chemicals on theHLA-B27gene promoter.Methods.Promoter reporter transfectants 293T-HLA-B27 and HeLa-HLA-B27 were tested using robotics with 12,264 chemicals. Chemicals that modulatedHLA-B27promoter activity > 150% or < 40% were selected for further evaluation of IC50/EC50 and cell viability.Results.The primary screening using the 293T-HLA-B27 promoter reporter cell line yielded 5.1% hits that either suppressed (556 chemicals) or enhanced (68 chemicals) theHLA-B27promoter activity. A secondary reconfirmation screening was carried out with these 624 candidates using HeLa-HLA-B27 promoter reporter cells under several different culture conditions. The yield of positive candidates was 130, of which 47 were derived from natural products. Based on the bio-information of those positive natural products, 21 chemicals were selected for analysis by dose-response IC50/EC50 experiments. Eight compounds showed potential pharmacological activities. Two suppressors are both derived from an herbal medicine (lei gong teng) that has been used for decades to treat immune diseases. The 6 activators all belonged to a group of chemicals known as flavonoids, widely distributed among dietary fruits and vegetables.Conclusion.Several common dietary products that contain certain flavonoids might be environmental risk factors for AS; the Chinese traditional herblei gong tengmight be a potential drug for patients who areHLA-B27-positive. These results provide new research directions for the pathogenesis and therapeutics of AS.

scholarly journals Canvass: A Crowd-Sourced, Natural Product Screening Library for Exploring Biological Space

2018 ◽  
Author(s):  
Sara E. Kearney ◽  
Gergely Zahoránszky-Kőhalmi ◽  
Kyle R. Brimacombe ◽  
Mark J. Henderson ◽  
Caitlin Lynch ◽  
...  
Keyword(s):  
Natural Products ◽  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Structural Diversity ◽  
Biological Evaluation ◽  
Structural Class ◽  
Differential Behavior ◽  
Biological Potential ◽  
Approved Drugs

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (–)-2(<i>S</i>)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

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