CANDI: a web server for predicting molecular targets and pathways of cannabis-based therapeutics

Journal of Cannabis Research, Год журнала: 2025, Номер 7(1)

Опубликована: Фев. 27, 2025

Abstract Background Cannabis sativa L. with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets mechanisms underlying synergistic effects diverse phytochemical constituents remain elusive. Understanding these is crucial developing targeted, effective cannabis-based therapies. Methods To investigate pathways involved cannabis compounds, we utilized DRIFT, deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts plant-based formulations. Predicted were then mapped Reactome pathway database identify biological processes affected. facilitate prediction associated any user-specified formulation, developed CANDI (Cannabis-derived compound Analysis Network Discovery Interface), web-based server. This platform offers user-friendly interface researchers drug developers explore compounds. Results Our analysis using DRIFT successfully identified numerous many which are relevant other diseases. The server enables affected providing valuable insights targeted Conclusions By combining computational approaches knowledge have server, tool allows us harness compounds treatment disorders. bridging pharmaceutical development medicine, propose novel approach botanical-based modalities.

Язык: Английский

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CANDI: A Web Server for Predicting Molecular Targets and Pathways of Cannabis-Based Therapeutics

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 9, 2024

Background: Cannabis sativa with a rich history of traditional medicinal use, has garnered significant attention in contemporary research for its potential therapeutic applications various human diseases, including pain, inflammation, cancer, and osteoarthritis. However, the specific molecular targets mechanisms underlying synergistic effects diverse phytochemical constituents remain elusive. Understanding these is crucial developing targeted, effective cannabis-based therapies. Methods: To investigate pathways involved cannabis compounds, we utilized DRIFT, deep learning model that leverages attention-based neural networks to predict compound-target interactions. We considered both whole plant extracts plant-based formulations. Predicted were then mapped Reactome pathway database identify biological processes affected. facilitate prediction associated any user-specified formulation, developed CANDI (Cannabis-derived compound Analysis Network Discovery Interface), web-based server. This platform offers user-friendly interface researchers drug developers explore compounds. Results: Our analysis using DRIFT successfully identified numerous many which are relevant other diseases. The server enables affected providing valuable insights targeted Conclusions: By combining computational approaches knowledge have server, tool allows us harness compounds treatment disorders. bridging pharmaceutical development medicine, propose novel approach botanical-based modalities.

Язык: Английский

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Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia

Antioxidants, Год журнала: 2024, Номер 13(9), С. 1072 - 1072

Опубликована: Сен. 2, 2024

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital limiting neurodegeneration, with its activation shown mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects a TAU-dependent FTD mouse model, reducing This suggests DMF repositioning potential for treatment. Until now, trial had been conducted analyze effect of on TDP-43-dependent FTD. In this study, we aimed determine efficacy TDP-43-related model that exhibits early cognitive impairment. Mice received oral every other day from presymptomatic symptomatic stages. By post-natal (PND) 60, improvement function already evident, becoming even more pronounced by PND90. enhancement correlates neuroprotection observed dentate gyrus reduction astrogliosis stratum lacunosum-moleculare zone. At prefrontal cortex (PFC) level, also observed, accompanied astrogliosis. Collectively, our results suggest application patients

Язык: Английский

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Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche’s Endocannabinoid System Projects

CHIMIA International Journal for Chemistry, Год журнала: 2024, Номер 78(7-8), С. 499 - 512

Опубликована: Авг. 21, 2024

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, associated receptors. It integral to maintaining homeostasis orchestrating key functions within the central nervous immune systems. Given its therapeutic significance, we have launched series drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid types 1 (CB1R) 2 (CB2R), monoacylglycerol lipase (MAGL), addressing wide array medical needs. pursuit new agents has been enhanced by creation specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, establishment biomarkers for engagement. By fusing medicinal chemistry with biology comprehensive, translational end-to-end strategy, expedited development novel therapeutics. Additionally, this strategy promises foster highly productive partnerships between industry academia, as will be illustrated through various examples.

Язык: Английский

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Progress in the role and mechanism of TDP-43

New discovery., Год журнала: 2024, Номер unknown, С. 1 - 8

Опубликована: Сен. 20, 2024

Background: TAR DNA-binding protein 43 kDa (TDP-43) has been shown to play an important role in the development of neurodegenerative diseases, but mechanism is still under study. Methods: By utilizing “TDP43”, “disease”, and “mechanism” as keywords, 200 related studies were retrieved downloaded from Pubmed database, including 60 articles. We summarized progress understanding TDP-43 over past two years, focusing on disease systems classification upstream downstream, connection, improvement, formation. Results: TDP-43, when abnormally aggregated, phosphorylated, or mislocalized, plays a key pathological diseases. Additionally, its impact normal reproductive cell formation, development, quantity, activity, well insulin secretion activation intestinal epithelial necrosis, should not be overlooked. Mechanistically, we identified relationship between expression factors, Enterovirus D68 (EV-D68), Heterogeneous Nuclear Ribonucleoprotein D (HNRNPD AUF1), Endoplasmic Reticulum Protein 57 (ERp57), Progranulin (PGRN), downstream factors such Meiotic Recombination Spo11 (Spo11), AMP-Activated Kinase (AMPK), Double-Strand-Break Repair Rad21 Homolog (Rad21L), IκB (IKK), TDP-43. Conclusion: neurodegeneration, which, phosphorylation, EV-d68, HNRNPD.

Язык: Английский

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Chemical Probes for Investigating the Endocannabinoid System

Current topics in behavioral neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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