RNA sequencing in a penile cancer cohort: an investigation of biomarkers of cisplatin resistance and potential therapeutic drug targets

Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear. Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrugresistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens. Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis. Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets. Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection. Bangladesh Journal of Medical Science Vol.20(4) 2021 p.887-896

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Accelerating Drug Discovery by Early Protein Drug Target Prediction Based on a Multi-Fingerprint Similarity Search †

Molecules ◽

10.3390/molecules24122233 ◽

2019 ◽

Vol 24 (12) ◽

pp. 2233 ◽

Cited By ~ 11

Author(s):

Michele Montaruli ◽

Domenico Alberga ◽

Fulvio Ciriaco ◽

Daniela Trisciuzzi ◽

Anna Rita Tondo ◽

...

Keyword(s):

Drug Discovery ◽

Small Molecules ◽

Similarity Search ◽

Drug Targets ◽

Search Algorithm ◽

Confidence Score ◽

Database Management System ◽

Therapeutic Drug ◽

Protein Drug ◽

Early Protein

In this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which included more than half a million high-quality small molecules extracted from the latest release of ChEMBL (version 24.1, at the time of writing). Provided with a high biological assay confidence score, these selected compounds explored up to 2822 protein drug targets. To improve the data accuracy, samples marked as prodrugs or with equivocal biological annotations were not considered. Notably, MuSSel performances were overall improved by using an object-relational database management system based on PostgreSQL. In order to challenge the real effectiveness of MuSSel in predicting relevant therapeutic drug targets, we analyzed a pool of 36 external bioactive compounds published in the Journal of Medicinal Chemistry from October to December 2018. This study demonstrates that the use of highly curated chemical and biological experimental data on one side, and a powerful multi-fingerprint search algorithm on the other, can be of the utmost importance in addressing the fate of newly conceived small molecules, by strongly reducing the attrition of early phases of drug discovery programs.

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Single-Cell RNA Sequencing of Blood and Ileal T Cells From Patients With Crohn's Disease Reveals Tissue-Specific Characteristics and Drug Targets

Gastroenterology ◽

10.1053/j.gastro.2018.10.046 ◽

2019 ◽

Vol 156 (3) ◽

pp. 812-815.e22 ◽

Cited By ~ 24

Author(s):

Werna T. Uniken Venema ◽

Michiel D. Voskuil ◽

Arnau Vich Vila ◽

Gerben van der Vries ◽

Bernadien H. Jansen ◽

...

Keyword(s):

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Single Cell ◽

Rna Sequencing ◽

Drug Targets ◽

Tissue Specific ◽

Single Cell Rna Sequencing

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Neuropeptide Y and its receptors as potential therapeutic drug targets

Clinica Chimica Acta ◽

10.1016/s0009-8981(02)00301-7 ◽

2002 ◽

Vol 326 (1-2) ◽

pp. 3-25 ◽

Cited By ~ 113

Author(s):

Antonio P Silva ◽

Claudia Cavadas ◽

Eric Grouzmann

Keyword(s):

Neuropeptide Y ◽

Drug Targets ◽

Therapeutic Drug

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Perivascular aquaporins: Potential postischemic therapeutic drug targets?*

Critical Care Medicine ◽

10.1097/ccm.0b013e3181833fb0 ◽

2008 ◽

Vol 36 (9) ◽

pp. 2701-2702 ◽

Cited By ~ 1

Author(s):

Douglas D. Fraser ◽

R David Andrew

Keyword(s):

Drug Targets ◽

Therapeutic Drug

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Ageing impairs the airway epithelium defence response to SARS-CoV-2

10.1101/2021.04.05.437453 ◽

2021 ◽

Author(s):

Alexander Capraro ◽

Sharon L Wong ◽

Anurag Adhikari ◽

Katelin M Allan ◽

Hardip R Patel ◽

...

Keyword(s):

Older Adults ◽

Young Adults ◽

Viral Replication ◽

Drug Targets ◽

Molecular Mechanisms ◽

Defence Response ◽

Nasal Epithelium ◽

Therapeutic Drug ◽

Healthy Children ◽

Age Related

AbstractAge-dependent differences in the clinical response to SARS-CoV-2 infection is well-documented1–3 however the underlying molecular mechanisms involved are poorly understood. We infected fully differentiated human nasal epithelium cultures derived from healthy children (1-12 years old), young adults (26-34 years old) and older adults (56-62 years old) with SARS-COV-2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host defence response. We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic drug targets. Viral load was lowest in infected older adult cultures despite the highest expression of SARS-CoV-2 entry and detection factors. We showed this was likely due to lower expression of hijacked host machinery essential for viral replication. Unlike the nasal epithelium of young adults and children, global host response and induction of the interferon signalling was profoundly impaired in older adults, which preferentially expressed proinflammatory cytokines mirroring the “cytokine storm” seen in severe COVID-194,5. In silico screening of our virus-host-drug network identified drug classes with higher efficacy in older adults. Collectively, our data suggests that cellular alterations that occur during ageing impact the ability for the host nasal epithelium to respond to SARS-CoV-2 infection which could guide future therapeutic strategies.

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In Silico identification of potential drug targets by subtractive genome analysis of Enterococcus faecium DO

10.1101/2020.02.14.948232 ◽

2020 ◽

Author(s):

Marwah Karim ◽

MD Nazrul Islam ◽

G. M. Nurnabi Azad Jewel

Keyword(s):

Alcohol Dehydrogenase ◽

Enterococcus Faecium ◽

In Silico ◽

Drug Targets ◽

3D Structure ◽

Comparative Genomic ◽

Therapeutic Drug ◽

Potential Drug ◽

Novel Drug ◽

Potential Drug Targets

AbstractOnce believed to be a commensal bacteria, Enterococcus faecium has recently emerged as an important nosocomial pathogen worldwide. A recent outbreak of E. faecium unrevealed natural and in vitro resistance against a myriad of antibiotics namely ampicillin, gentamicin and vancomycin due to over-exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat demands the identification of new therapeutic targets to combat E. faecium infections.In this present study, comparative proteome analysis, subtractive genomic approach, metabolic pathway analysis and additional drug prioritizing parameters were used to propose a potential novel drug targets for E. faecium strain DO. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified a total of 207 putative target proteins in E. faecium DO that showed no similarity to human proteins. Among them 105 proteins were identified as essential novel proteins that could serve as potential drug targets through further bioinformatic approaches; such as-prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characterization. Eventually 19 non-homologous essential proteins of E. faecium DO were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets. Among these targets aldehyde-alcohol dehydrogenase was found to be involved in maximum pathways, and therefore, was chosen as novel drug target. Interestingly, aldehyde-alcohol dehydrogenase enzyme contains two domains namely acetaldehyde dehydrogenase and alcohol dehydrogenase, on which a 3D structure homology modeling and in silico molecular docking were performed. Finally, eight molecules were confirmed as the most suitable ligands for aldehyde-alcohol dehydrogenase and hence proposed as the potential inhibitors of this target.In conclusion, being human non-homologous, aldehyde-alcohol dehydrogenase protein can be targeted for potential therapeutic drug development in future. However, laboratory based experimental research should be performed to validate our findings in vivo.

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The Role of Deubiquitinating Enzymes in Hematopoiesis and Hematological Malignancies

10.20944/preprints202003.0054.v1 ◽

2020 ◽

Author(s):

Neha Sarodaya ◽

Janardhan Karapurkar ◽

Kye-Seong Kim ◽

Seok-Ho Hong ◽

Suresh Ramakrishna

Keyword(s):

Drug Targets ◽

Molecular Mechanisms ◽

Human Life ◽

Therapeutic Drug ◽

Cellular Interactions ◽

Deubiquitinating Enzymes ◽

Hematopoietic Stem ◽

Hematological Disorders ◽

Additional Information

Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human life span. Single HSCs can give rise to at least eight distinct blood cell lineages. Together, hematopoiesis, erythropoiesis and angiogenesis coordinate several biological processes, such as cellular interactions in development and proliferation, guided migration, lineage programming and reprogramming by transcription factors. Any dysregulation of these processes may result in hematological disorders and/or malignancies. Several studies of the molecular mechanisms governing HSC maintenance have demonstrated that protein regulation by the ubiquitin proteasomal pathway is crucial for normal HSC function. Recent studies have shown that the reversal of ubiquitination by deubiquitinating enzymes (DUBs) plays an equally important role in hematopoiesis; however, there is only limited additional information regarding the biological function of DUBs. In this review, we focus on recent discoveries that have led to a better understanding of the physiological roles of DUBs in hematopoiesis, erythropoiesis and angiogenesis. In addition, we discuss the DUBs associated with common hematological disorders and malignancies, which may potentially be therapeutic drug targets.

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