Pain-CKB, A Pain-Domain-Specific Chemogenomics Knowledgebase for Target Identification and Systems Pharmacology Research

Feng, Zhiwei; Chen, Maozi; Shen, Mingzhe; Liang, Tianjian; Chen, Hui; Xie, Xiang‐Qun

doi:10.1021/acs.jcim.0c00633

Cited by 4 publications

(7 citation statements)

References 30 publications

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“…To facilitate pain research, we have constructed the pain domain-specific chemogenomics knowledgebase (Pain-CKB) . Pain-CKB is also equipped with various chemoinformatics tools like HTDocking, TargetHunter, Spider Plot, and BBB predictor to provide public users with cloud computing services for target identification and systems pharmacology research.…”

Section: Resultsmentioning

confidence: 99%

“…Herein, we have constructed the pain domain-specific chemogenomics knowledgebase (Pain-CKB) based on our previously established molecular information databases − in order to accelerate the research in pain-related areas. The knowledgebase assembles a large amount of analgesic information and pain-related protein targets extracted from the literature.…”

Section: Introductionmentioning

confidence: 99%

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Pain Chemogenomics Knowledgebase (Pain-CKB) for Systems Pharmacology Target Mapping and Physiologically Based Pharmacokinetic Modeling Investigation of Opioid Drug–Drug Interactions

Shen

Chen

Liang

et al. 2020

ACS Chem. Neurosci.

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More than 50 million adults in America suffer from chronic pain. Opioids are commonly prescribed for their effectiveness in relieving many types of pain. However, excessive prescribing of opioids can lead to abuse, addiction, and death. Non-steroidal anti-inflammatory drugs (NSAIDs), another major class of analgesic, also have many problematic side effects including headache, dizziness, vomiting, diarrhea, nausea, constipation, reduced appetite, and drowsiness. There is an urgent need for the understanding of molecular mechanisms that underlie drug abuse and addiction to aid in the design of new preventive or therapeutic agents for pain management. To facilitate pain related small-molecule signaling pathway studies and the prediction of potential therapeutic target(s) for the treatment of pain, we have constructed a comprehensive platform of a pain domain-specific chemogenomics knowledgebase (Pain-CKB) with integrated data mining computing tools. Our new computing platform describes the chemical molecules, genes, proteins, and signaling pathways involved in pain regulation. Pain-CKB is implemented with a friendly user interface for the prediction of the relevant protein targets and analysis and visualization of the outputs, including HTDocking, TargetHunter, BBB predictor, and Spider Plot. Combining these with other novel tools, we performed three case studies to systematically demonstrate how further studies can be conducted based on the data generated from Pain-CKB and its algorithms and tools. First, systems pharmacology target mapping was carried out for four FDA approved analgesics in order to identify the known target and predict off-target interactions. Subsequently, the target mapping outcomes were applied to build physiologically based pharmacokinetic (PBPK) models for acetaminophen and fentanyl to explore the drug−drug interaction (DDI) between this pair of drugs. Finally, pharmaco-analytics was conducted to explore the detailed interaction pattern of acetaminophen reactive metabolite and its hepatotoxicity target, thioredoxin reductase.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pain Chemogenomics Knowledgebase (Pain-CKB) for Systems Pharmacology Target Mapping and Physiologically Based Pharmacokinetic Modeling Investigation of Opioid Drug–Drug Interactions

Shen

Chen

Liang

et al. 2020

ACS Chem. Neurosci.

Self Cite

View full text Add to dashboard Cite

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“…ASD [60] is one example that files allosteric modulators and related macromolecules to facilitate the research on allosteric modulation. The rising of Chemogenomics databases [61,62] for certain diseases and druggable targets is another example that these libraries focus on particular areas of research. Usually, these target and disease-focused Chemogenomics databases integrate both target and chemical information with computing tools for systems pharmacology research.…”

Section: Data Sources and Machine Learning Infrastructuresmentioning

confidence: 99%

“…Usually, these target and disease-focused Chemogenomics databases integrate both target and chemical information with computing tools for systems pharmacology research. Pain-CKB [61], for example, it is a pain-domain-specific knowledgebase describes the chemical molecules, genes, and proteins involved in pain regulation.…”

Section: Data Sources and Machine Learning Infrastructuresmentioning

confidence: 99%

Generative chemistry: drug discovery with deep learning generative models

Bian

Xie

2021

J Mol Model

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The de novo design of molecular structures using deep learning generative models introduces an encouraging solution to drug discovery in the face of the continuously increased cost of new drug development. From the generation of original texts, images, and videos, to the scratching of novel molecular structures the creativity of deep learning generative models exhibits the height machine intelligence can achieve. The purpose of this paper is to review the latest advances in generative chemistry which relies on generative modeling to expedite the drug discovery process. This review starts with a brief history of artificial intelligence in drug discovery to outline this emerging paradigm. Commonly used chemical databases, molecular representations, and tools in cheminformatics and machine learning are covered as the infrastructure for generative chemistry. The detailed discussions on utilizing cutting-edge generative architectures, including recurrent neural network, variational autoencoder, adversarial autoencoder, and generative adversarial network for compound generation are focused. Challenges and future perspectives follow.

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“…Besides the clinical applications, researchers have employed ML methods at the early stages of analgesic discovery, such as identifying novel genes and pathways associated with acute and chronic pain 451 and predicting inhibitors of a drug target for pain (i.e., NaV1.7 sodium channel) 452 . To facilitate the prediction of novel multi‐target analgesics or drug combinations for pain treatment, researchers have established a comprehensive pain‐domain‐specific chemogenomics knowledgebase that includes the analgesics in current use, pain‐related targets with all available 3D structures, and the compounds reported for these target proteins 453 …”

Section: Ai/ml Applications In Cns Drug Discoverymentioning

confidence: 99%

Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions

Vatansever

Schlessinger

Wacker

et al. 2020

Medicinal Research Reviews

217

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Neurological disorders significantly outnumber diseases in other therapeutic areas. However, developing drugs for central nervous system (CNS) disorders remains the most challenging area in drug discovery, accompanied with the long timelines and high attrition rates. With the rapid growth of biomedical data enabled by advanced experimental technologies, artificial intelligence (AI) and machine learning (ML) have emerged as an indispensable tool to draw meaningful insights and improve decision making in drug discovery. Thanks to the advancements in AI and ML algorithms, now the AI/ML‐driven solutions have an unprecedented potential to accelerate the process of CNS drug discovery with better success rate. In this review, we comprehensively summarize AI/ML‐powered pharmaceutical discovery efforts and their implementations in the CNS area. After introducing the AI/ML models as well as the conceptualization and data preparation, we outline the applications of AI/ML technologies to several key procedures in drug discovery, including target identification, compound screening, hit/lead generation and optimization, drug response and synergy prediction, de novo drug design, and drug repurposing. We review the current state‐of‐the‐art of AI/ML‐guided CNS drug discovery, focusing on blood–brain barrier permeability prediction and implementation into therapeutic discovery for neurological diseases. Finally, we discuss the major challenges and limitations of current approaches and possible future directions that may provide resolutions to these difficulties.

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Pain-CKB, A Pain-Domain-Specific Chemogenomics Knowledgebase for Target Identification and Systems Pharmacology Research

Cited by 4 publications

References 30 publications

Pain Chemogenomics Knowledgebase (Pain-CKB) for Systems Pharmacology Target Mapping and Physiologically Based Pharmacokinetic Modeling Investigation of Opioid Drug–Drug Interactions

Pain Chemogenomics Knowledgebase (Pain-CKB) for Systems Pharmacology Target Mapping and Physiologically Based Pharmacokinetic Modeling Investigation of Opioid Drug–Drug Interactions

Generative chemistry: drug discovery with deep learning generative models

Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions

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