摘要
背景:尽管不断努力开发新的治疗方法,但迫切需要发现新的药物来治疗对现有药物表现出原发性或继发性耐药性的肿瘤。源自患者来源的原位异种移植物的细胞培养物是有希望的临床前模型,可以更好地预测癌症复发中的药物反应。 目的:本研究的目的是研究药物的理化性质与其体外效力之间的关系,并确定偏向于此类药物的选择性或混杂性的化学支架。 方法:考虑了针对来自 30 个癌症原位患者衍生异种移植 (O-PDX) 模型的细胞培养物筛选的 158 种药物的生物活性。药物由物理化学描述符和化学结构指纹表示。监督学习被用来模拟特征和体外效力之间的关系。 结果:对肺泡横纹肌肉瘤和骨肉瘤具有体外效力的药物往往具有更多的环数、两个碳-杂键和卤素。确定了这些表型目标的选择性和混杂支架。在这 30 个目标中获得了体外效力的高度预测模型,可以通过网络服务器 (https://rnewbie.shinyapps.io/Shobek-master) 将其应用于看不见的分子。 结论:有可能识别特殊的化学支架并预测这 30 个靶标中看不见的分子的体外效力。这些信息和模型应该有助于选择哪些分子来筛选这些小儿实体瘤的原代培养物。
关键词: 化学信息学、数据挖掘、儿科癌症、源自患者的异种移植物、机器学习、QSAR。
Current Medicinal Chemistry
Title:Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
Volume: 28 Issue: 38
关键词: 化学信息学、数据挖掘、儿科癌症、源自患者的异种移植物、机器学习、QSAR。
摘要:
Background: Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumors exhibiting primary or secondary resistance to existing drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence.
Objective: The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biasedtowards selectivity or promiscuity of such drugs.
Methods: The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency.
Results: Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver (https://rnewbie.shinyapps.io/Shobek-master).
Conclusion: It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.
Export Options
About this article
Cite this article as:
Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors, Current Medicinal Chemistry 2021; 28 (38) . https://dx.doi.org/10.2174/0929867328666210419134708
DOI https://dx.doi.org/10.2174/0929867328666210419134708 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Iron Chelators in Cancer Chemotherapy
Current Topics in Medicinal Chemistry DprE1 - from the Discovery to the Promising Tuberculosis Drug Target
Current Pharmaceutical Design Radiosynthesis of 2-deoxy-2-[18F]fluorothymidine ([18F]FT), a Putative PET Agent for Imaging HSV-TK Expression
Current Radiopharmaceuticals The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Current Molecular Medicine The Shielding Action of Disaccharides for Typical Proteins in Aqueous Solution Against Static, 50 Hz and 1800 MHz Frequencies Electromagnetic Fields
Current Chemical Biology Extraction, Isolation and Analysis of Chondroitin Sulfate Glycosaminoglycans
Recent Patents on Food, Nutrition & Agriculture Bioinformatics Tools for Mass Spectroscopy-Based Metabolomic Data Processing and Analysis
Current Bioinformatics High Throughput Automated Determination of Glutathione Based on the Formation of a UV-Absorbing Thioacrylate Derivative
Combinatorial Chemistry & High Throughput Screening DNA as Platform for New Biomaterials. Metal-Containing Nucleic Acids
Current Organic Chemistry Actinium-225 in Targeted Alpha-Particle Therapeutic Applications
Current Radiopharmaceuticals Sensoring Strategies Using Quantum Dots: A Critical View
Current Organic Chemistry Effect of the Metal Center on the Antitumor Activity of the Analogous Dinuclear Spermine Chelates (PdCl2)2(Spermine) and (PtCl2)2(Spermine)
Letters in Drug Design & Discovery Hydroxytyrosol and Derivatives: Isolation, Synthesis, and Biological Properties
Current Organic Chemistry Cancer Kinases and its Novel Inhibitors: Past, Present and Future Challenges
Current Drug Targets Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate
Current Cancer Drug Targets Capillary Zone Electrophoresis for Separation and Quantitative Determination of Mexiletine and its Main Phase I Metabolites
Drug Metabolism Letters Unleashing the Potential of Microbial Natural Products in Drug Discovery: Focusing on <i>Streptomyces</i> as Antimicrobials Goldmine
Current Topics in Medicinal Chemistry Headspace Gas Chromatography Methods and their Potential Industrial Applications
Current Chromatography Stabilization of Folding Intermediate States from Alkaline Induced Unfolded State of Bovine Serum Fetuin in Trifluoroethanol and Acetonitrile
Protein & Peptide Letters False Positives in the Early Stages of Drug Discovery
Current Medicinal Chemistry