scholarly journals A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics

2021 ◽  
Author(s):  
Jonas Gossen ◽  
Simone Albani ◽  
Anton Hanke ◽  
Benjamin P. Joseph ◽  
Cathrine Bergh ◽  
...  
Keyword(s):  
Protein Dynamics ◽  
Library Screening ◽  
Compound Library ◽  
High Affinity

scholarly journals Discovery of a new lead compound for plant growth retardants through compound library screening

2014 ◽  
Vol 39 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Keimei Oh ◽  
Tadashi Matsumoto ◽  
Tomoki Hoshi ◽  
Yuko Yoshizawa
Keyword(s):  
Plant Growth ◽  
Library Screening ◽  
Lead Compound ◽  
Compound Library ◽  
Growth Retardants ◽  
Plant Growth Retardants

scholarly journals HDAC6 Inhibitors Sensitize Claudin-high Breast Cancer Cells to Cysteine Depletion via Activation of PKCγ Signaling

2020 ◽  
Author(s):  
Tahiyat Alothaim ◽  
Morgan Charbonneau ◽  
Xiaohu Tang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Death ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Zinc Homeostasis ◽  
Cancer Type ◽  
Library Screening ◽  
Compound Library ◽  
Breast Tumor Cells

Abstract IntroductionTriple-negative breast cancer (TNBC) is a highly malignant breast cancer type with poor prognosis and lacks effective therapy. TNBC is not responsive to targeted therapy for hormone receptors and often exhibit resistance to current chemotherapeutic agents. Targeting tumor metabolism is an emergent strategy to treat cancer. Therefore, identification of tumor metabolic deregulations and development of effective targeted therapies are urgently needed.MethodsWe performed the epigenetic compound library screening in claudin-high breast tumor cells and identified therapeutical sensitizers to overcome the drug resistance of targeted cysteine-dependence therapy. Gene expression profiling were generated to analyze signaling pathways induced by the combined tubacin and cysteine deprivation treatment. Specific inhibitors, shRNA, and CRISPR/Cas9 gene editing approaches were used to target cellular proteins HDAC6 and PKCγ and examine their roles in cell death. Cell viability, RT-qPCR, and Western blotting assays were performed in cysteine-independent tumor cells to examine the anticancer effects of combined tubacin and cysteine deprivation treatment. ResultsWe found that TNBC has differential death responses to cysteine deprivation and the cysteine-dependence of TNBC corelates with the expression levels of claudin genes in addition to the classical EMT markers. To overcome drug resistance in claudin-high/cysteine-independent breast tumor cells, HDAC6 inhibitors were identified by the epigenetic compound library screening as potent sensitizers that synergize with cysteine deprivation to eradicate cysteine-independent tumor cells. Unexpectedly, HDAC6 knockout did not recapitulate the HDAC6 inhibitors-mediated synthetic lethality, indicating that HDAC6 is not the actual target of HDAC6 inhibitors in this context. Transcriptomic profiling revealed that HDAC6 inhibitors synergizes with cysteine depletion to trigger a profound gene transcriptional program. Notably, a zinc-related gene response was observed to accompany with a prominent increase of labile zinc in cells during cell death. We further showed that activation of PKCγ signaling is required to interfere cellular zinc homeostasis and drive HDAC6 inhibitors-mediated cell death.ConclusionOur study demonstrated that HDAC6 inhibitors function as potent sensitizers to overcome the resistance of cysteine deprivation in claudin-high breast tumor cells. Identification of such sensitizers would make the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.

scholarly journals Correction: A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria.

2020 ◽  
Vol 295 (17) ◽  
pp. 5835-5835 ◽  
Author(s):  
Helen L. Scott ◽  
Nicola Buckner ◽  
Francesc Fernandez-Albert ◽  
Elisa Pedone ◽  
Lorena Postiglione ◽  
...  
Keyword(s):  
Library Screening ◽  
Compound Library ◽  
Screening Approach ◽  
Genome Wide ◽  
Druggable Genome

scholarly journals Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

Circulation ◽  
2020 ◽  
Vol 141 (9) ◽  
pp. 751-767 ◽  
Author(s):  
Katharina Schimmel ◽  
Mira Jung ◽  
Ariana Foinquinos ◽  
Gorka San José ◽  
Javier Beaumont ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Natural Compound ◽  
Cardiac Fibrosis ◽  
Library Screening ◽  
Compound Library
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