Differential analysis of Orientia tsutsugamushi genomes for therapeutic target identification and possible intervention through natural product inhibitor screening

2021 ◽  
pp. 105165
Author(s):  
Zarrin Basharat ◽  
Umaimah Akhtar ◽  
Kanwal Khan ◽  
Ghallab Alotaibi ◽  
Khurshid Jalal ◽  
...  
Keyword(s):  
Natural Product ◽  
Therapeutic Target ◽  
Target Identification ◽  
Differential Analysis ◽  
Orientia Tsutsugamushi ◽  
Inhibitor Screening

scholarly journals RNAi screen for rapid therapeutic target identification in leukemia patients

2009 ◽  
Vol 106 (21) ◽  
pp. 8695-8700 ◽  
Author(s):  
J. W. Tyner ◽  
M. W. Deininger ◽  
M. M. Loriaux ◽  
B. H. Chang ◽  
J. R. Gotlib ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Target Identification ◽  
Rnai Screen

scholarly journals Some Perspectives on Network Modeling in Therapeutic Target Prediction

2013 ◽  
Vol 5 ◽  
pp. BECB.S10793 ◽  
Author(s):  
Reka Albert ◽  
Bhaskar DasGupta ◽  
Nasim Mobasheri
Keyword(s):  
Therapeutic Target ◽  
Drug Target ◽  
Biological Network ◽  
Target Identification ◽  
Target Prediction ◽  
Identification Problem ◽  
Pharmaceutical Companies ◽  
Specific Behavior ◽  
Drug Target Identification ◽  
Key Steps

Drug target identification is of significant commercial interest to pharmaceutical companies, and there is a vast amount of research done related to the topic of therapeutic target identification. Interdisciplinary research in this area involves both the biological network community and the graph algorithms community. Key steps of a typical therapeutic target identification problem include synthesizing or inferring the complex network of interactions relevant to the disease, connecting this network to the disease-specific behavior, and predicting which components are key mediators of the behavior. All of these steps involve graph theoretical or graph algorithmic aspects. In this perspective, we provide modelling and algorithmic perspectives for therapeutic target identification and highlight a number of algorithmic advances, which have gotten relatively little attention so far, with the hope of strengthening the ties between these two research communities.

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 Targeting Autophagy Peptidase ATG4B With A Novel Natural Product Inhibitor Azalomycin F4a For Advanced Gastric Cancer

2021 ◽  
Author(s):  
Lin Zhong ◽  
Bin Yang ◽  
Zhenhua zhang ◽  
Xiaojuan Wang ◽  
Yinfeng Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Natural Product ◽  
Advanced Gastric Cancer ◽  
Therapeutic Target ◽  
Marine Natural Product ◽  
Migration And Invasion ◽  
Enzyme Activity Assay ◽  
Cell Viability Assay

Abstract Background: Advanced gastric cancer (GCa) remains highly lethal due to the lack of effective therapies. Identifying promising therapeutic targets and developing effective treatment against GCa are urgently needed. Here, we investigated whether Autophagy-related gene 4B (ATG4B) could be a potential therapeutic target against GCa and identified marine natural product Azalomycin F4a (Am-F4a) as a potent ATG4B inhibitor and a potential anticancer agent. Methods: The expression of ATG4B in clinical GCa tumor specimens were examined by immunoblotting and interrogation of public databases. The association between ATG4B expression and patient’s survival was assessed. FRET, surface plasmon resonance, transmission electron microscopy analysis, enzyme activity assay and compute docking were used to assess the binding and inhibition of ATG4B by Am-F4a. RNA interference, inhibitors, CCK-8 cell viability assay, colony formation, apoptosis assay, wound-healing, transwell invasion assay, western blotting and Patient-derived organoids were used to assess the role of ATG4B in GCa cells. GCa cell-derived xenograft models, patient-derived xenografts and orthotopic metastasis xenografts were used to evaluate the anti-tumor growth and anti-metastasis effects of Am-F4a alone or in combination with 5-FU in vivo.Results: ATG4B was highly upregulated in GCa tumors. Its high expression was associated with patient’s poor prognosis. knockdown of ATG4B significantly inhibited GCa cell survival and tumor growth. Am-F4a was identified as a novel and potent ATG4B inhibitor. Am-F4a effectively inhibited GCa cell autophagy and growth via targeting ATG4B both in vitro and in vivo. Besides, both pharmacological inhibition and knockdown of ATG4B significantly suppressed GCa cell migration and invasion. Am-F4a potently blocked the metastasis of primary GCa tumors and effectively sensitized tumors to chemotherapy.Conclusion: These findings indicate that ATG4B is a potential novel therapeutic target against GCa and that the natural product Am-F4a is a novel ATG4B inhibitor that can be further developed for treatment of GCa.

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