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1.
Mar Drugs ; 19(2)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494402

RESUMO

The review of the 2016-2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016-2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016-2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Sistema Imunitário/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Antituberculosos/química , Antituberculosos/isolamento & purificação , Antituberculosos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Organismos Aquáticos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Sistema Imunitário/fisiologia , Fenômenos Farmacológicos e Toxicológicos
2.
Cell Rep ; 33(3): 108296, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33086069

RESUMO

CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB/) integrates drug sensitivity and genomic data, including high-resolution methylome and transcriptome from 118 patient-derived small cell lung cancer (SCLC) cell lines, providing a resource for research into this "recalcitrant cancer." We demonstrate the reproducibility and stability of data from multiple sources and validate the SCLC consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ASCL1, POU2F3, and YAP1. Our analyses reveal transcription networks linking SCLC subtypes with MYC and its paralogs and the NOTCH and HIPPO pathways. SCLC subsets express specific surface markers, providing potential opportunities for antibody-based targeted therapies. YAP1-driven SCLCs are notable for differential expression of the NOTCH pathway, epithelial-mesenchymal transition (EMT), and antigen-presenting machinery (APM) genes and sensitivity to mTOR and AKT inhibitors. These analyses provide insights into SCLC biology and a framework for future investigations into subtype-specific SCLC vulnerabilities.


Assuntos
Mineração de Dados/métodos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Algoritmos , Linhagem Celular Tumoral , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica/métodos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Genômica/métodos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Fenômenos Farmacológicos e Toxicológicos , Reprodutibilidade dos Testes , Software , Fatores de Transcrição/genética
3.
Crit Rev Biotechnol ; 40(2): 213-230, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31906727

RESUMO

Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.


Assuntos
Dispositivos Lab-On-A-Chip , Doenças Respiratórias/fisiopatologia , Animais , Pesquisa Biomédica , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Modelos Biológicos , Fenômenos Farmacológicos e Toxicológicos , Impressão Tridimensional , Doenças Respiratórias/tratamento farmacológico , Engenharia Tecidual
4.
J Clin Pharmacol ; 59 Suppl 1: S87-S94, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502687

RESUMO

Challenges in pediatric drug development include small patient numbers, limited outcomes research, ethical barriers, and sparse biosamples. Increasingly, pediatric drug development is focusing on extrapolation: leveraging knowledge about adult disease and drug responses to inform projections of drug and clinical trial performance in pediatric subpopulations. Pharmacokinetic-pharmacodynamic (PK-PD) modeling and extrapolation aim to reduce the numbers of patients and data points needed to establish efficacy. Planning for PK-PD and biomarker studies should begin early in the adult drug development program. Extrapolation relies on the assumption that both the underlying disease and the mechanism of action of the drug used to treat that disease are similar in adults and pediatric subpopulations. Clearly, developmental changes in PK and PD need to be considered to enhance the quality of PK-PD modeling and, therefore, increase the success of extrapolation. This article focuses on the influence of differences in PD between adults and pediatric subpopulations that are highly relevant for the use of extrapolation.


Assuntos
Desenvolvimento de Medicamentos , Modelos Biológicos , Fenômenos Farmacológicos e Toxicológicos , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Farmacocinética
5.
Methods Mol Biol ; 2036: 317-339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410806

RESUMO

We describe tactics to assess pharmacokinetic (PK) and pharmacodynamic (PD) parameters of oligonucleotides. The chapter includes recommendations on the design of single-dose preclinical PK studies, preclinical PKPD studies, and toxicological studies, and on best practice for scaling PK and PD parameters from animal to human. We focus on single-stranded oligonucleotides, but relevant differences to double-stranded RNAs are also addressed.


Assuntos
Monitoramento de Medicamentos/métodos , Oligonucleotídeos/farmacocinética , Fenômenos Farmacológicos e Toxicológicos , Algoritmos , Humanos , Modelos Biológicos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/química , Projetos de Pesquisa
6.
Med Sci Monit ; 25: 6051-6073, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31409761

RESUMO

BACKGROUND Osteoarthritis (OA) affects the health and wellbeing of the elderly. Shaoyao Gancao decoction (SGD) is used in traditional Chinese medicine (TCM) for the treatment of OA and has two active components, shaoyao (SY) and gancao (GC). This study aimed to undertake a network pharmacology analysis of the mechanism of the effects of SGD in OA. MATERIAL AND METHODS The active compounds and candidates of SGD were obtained from the Traditional Chinese Medicine (TCM) Databases@Taiwan, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the STITCH database, the ChEMBL database, and PubChem. The network pharmacology approach involved network construction, target prediction, and module analysis. Significant signaling pathways of the cluster networks for SGD and OA were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS Twenty-three bioactive compounds were identified, corresponding to 226 targets for SGD. Also, 187 genes were closely associated with OA, of which 161 overlapped with the targets of SGD and were considered to be therapeutically relevant. Functional enrichment analysis suggested that SGD exerted its pharmacological effects in OA by modulating multiple pathways, including cell cycle, cell apoptosis, drug metabolism, inflammation, and immune modulation. CONCLUSIONS A novel approach was developed to systematically identify the mechanisms of the TCM, SGD in OA using network pharmacology analysis.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite/tratamento farmacológico , China , Cromatografia Líquida de Alta Pressão/métodos , Análise por Conglomerados , Simulação por Computador , Bases de Dados Factuais , Humanos , Medicina Tradicional Chinesa/métodos , Fenômenos Farmacológicos e Toxicológicos , Mapas de Interação de Proteínas
7.
Med Sci Monit ; 25: 5700-5716, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368456

RESUMO

d_abstr_R Rhizoma drynariae is the main traditional Chinese medicine used for the treatment of osteoporosis, but its anti-osteoporotic targeting mechanism has not been fully elucidated due to the complexity of its active ingredients. In this study, the pharmacological mechanism of action of Rhizoma drynariae against osteoporosis was studied by integrating pharmacological concepts. The pharmacokinetic characteristics of selected major active constituents of Rhizoma drynariae and the SMILES structural similarity were used to predict related targets. A literature search was conducted to identify known osteoporosis treatment targets, which were then combined with the predicted targets to construct the direct or indirect target interaction network map of Rhizoma drynariae against osteoporosis. Finally, data on the key targets of the interactions, ranked according to relevant node parameters obtained through pathway enrichment analysis and screening of key targets and active ingredients of Rhizoma drynariae, were used to perform molecular docking simulation. We screened 16 active ingredients of Rhizoma drynariae, and 7 key targets with direct or indirect effects with a high frequency were obtained. These main pathways were found to play important roles in the PI3k-akt signaling pathway, osteoclast differentiation, Wnt signaling pathway, and estrogen signaling pathway. Molecular docking showed that most active ingredients of Rhizoma drynariae had strong binding efficiency with key targets. Based on network pharmacology, we conclude that Rhizoma drynariae plays an anti-osteoporotic role by directly or indirectly targeting multiple major signaling pathways and influencing the proliferation and differentiation of multiple types of cells.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/tratamento farmacológico , China , Simulação por Computador , Bases de Dados Factuais , Desenvolvimento de Medicamentos/métodos , Humanos , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Farmacocinética , Fenômenos Farmacológicos e Toxicológicos , Polypodiaceae/metabolismo , Mapas de Interação de Proteínas
8.
Med Sci Monit ; 25: 5589-5593, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31352466

RESUMO

BACKGROUND The aim of our study was to elucidate the biological targets and pharmacological mechanisms for calycosin (CC) against colorectal cancer (CRC) through an approach of system pharmacology. MATERIAL AND METHODS Using a web-based platform, all CRC-causing genes were identified using a database of gene-disease associations (DisGeNET), and all well-known genes of CC identified using the databases of prediction of protein targets of small molecules (Swiss Target Prediction), drug classification, and target prediction (SuperPred). The carefully selected genes of CRC and CC were concurrently constructed by using a database of functional protein association networks (STRING), and use of software for visualizing complex networks (Cytoscape), characterized with production of protein-protein interaction (PPI) network of CC against CRC. The important biological targets of CC against CRC were identified through topological analysis, then the biological processes and molecular pathways of CC against CRC were further revealed for testing these important biotargets by enrichment assays. RESULTS We found that the key predictive targets of CC against CRC were estrogen receptor 2 (ESR2), ATP-binding cassette sub-family G member 2 (ABCG2), breast cancer type 1 susceptibility protein (BRCA1), estrogen receptor 1 (ESR1), cytochrome p450 19A1 (CYP19A1), and epidermal growth factor receptor (EGFR). Visual analysis revealed that the biological processes of CC against CRC were positively linked to hormonal metabolism, regulation of genes, transport, cell communication, and signal transduction. Further, the interrelated molecular pathways were chiefly related to endogenous nuclear estrogen receptor alpha network, forkhead box protein A1 (FOXA1) transcription factor network, activating transcription factor 2 (ATF2) transcription factor network, regulation of telomerase, plasma membrane estrogen receptor signaling, estrogen biosynthesis, androgen receptor, FOXA transcription factor networks, estrogen biosynthesis, and phosphorylation of repair proteins. CONCLUSIONS Use of system pharmacology revealed the biotargets, biological processes, and pharmacological pathways of CC against CRC. Intriguingly, the identifiable predictive biomolecules are likely potential targets for effectively treating CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Isoflavonas/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Aromatase/genética , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/fisiopatologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Receptores ErbB/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Isoflavonas/farmacologia , Proteínas de Neoplasias , Fenômenos Farmacológicos e Toxicológicos , Mapas de Interação de Proteínas/genética , Transdução de Sinais , Análise de Sistemas
9.
Clin Pharmacokinet ; 58(1): 39-52, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29675639

RESUMO

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies.


Assuntos
Desenvolvimento de Medicamentos , Modelos Biológicos , Farmacocinética , Fenômenos Farmacológicos e Toxicológicos , Criança , Desenvolvimento de Medicamentos/legislação & jurisprudência , Humanos , Legislação de Medicamentos
10.
Molecules ; 23(11)2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428514

RESUMO

The study is aimed at developing linear classifiers to predict the capacity of a given substrate to yield reactive metabolites. While most of the hitherto reported predictive models are based on the occurrence of known structural alerts (e.g., the presence of toxophoric groups), the present study is focused on the generation of predictive models involving linear combinations of physicochemical and stereo-electronic descriptors. The development of these models is carried out by using a novel classification approach based on enrichment factor optimization (EFO) as implemented in the VEGA suite of programs. The study took advantage of metabolic data as collected by manually curated analysis of the primary literature and published in the years 2004⁻2009. The learning set included 977 substrates among which 138 compounds yielded reactive first-generation metabolites, plus 212 substrates generating reactive metabolites in all generations (i.e., metabolic steps). The results emphasized the possibility of developing satisfactory predictive models especially when focusing on the first-generation reactive metabolites. The extensive comparison of the classifier approach presented here using a set of well-known algorithms implemented in Weka 3.8 revealed that the proposed EFO method compares with the best available approaches and offers two relevant benefits since it involves a limited number of descriptors and provides a score-based probability thus allowing a critical evaluation of the obtained results. The last analyses on non-cheminformatics UCI datasets emphasize the general applicability of the EFO approach, which conveniently performs using both balanced and unbalanced datasets.


Assuntos
Biotransformação , Aprendizado de Máquina , Modelos Estatísticos , Fenômenos Farmacológicos e Toxicológicos , Algoritmos
11.
Cell Syst ; 6(4): 424-443.e7, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29655704

RESUMO

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics.


Assuntos
Bases de Dados Factuais , Fosfoproteínas/efeitos dos fármacos , Algoritmos , Linhagem Celular , Cromatografia Líquida , Conjuntos de Dados como Assunto , Regulação da Expressão Gênica , Código das Histonas , Humanos , Espectrometria de Massas , Fenômenos Farmacológicos e Toxicológicos , Fosfoproteínas/metabolismo , Proteômica , Transdução de Sinais , Software
12.
Neurotoxicology ; 66: 204-212, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29428870

RESUMO

Physiological methods that can be similarly recorded in humans and animals have a major role in sensory toxicology, as they provide a bridge between human sensory perception data and the molecular and cellular data obtained in animal studies. Vestibular toxicity research lags well behind other sensory systems in many aspects, including the availability of methods for functional assessment in animals that could be robustly translated to human significance. Here we review the methods available for the assessment of vestibular function in both humans and laboratory animals, with an emphasis on their similarity or divergence, to highlight their potential utility for the predictive assessment of vestibular toxicity.


Assuntos
Doenças Vestibulares/induzido quimicamente , Doenças Vestibulares/diagnóstico , Testes de Função Vestibular/métodos , Animais , Humanos , Fenômenos Farmacológicos e Toxicológicos , Especificidade da Espécie , Toxicologia/métodos , Doenças Vestibulares/fisiopatologia , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/fisiopatologia
13.
PLoS One ; 12(3): e0174355, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28350814

RESUMO

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16ß-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Sistema Enzimático do Citocromo P-450/genética , Família 2 do Citocromo P450/genética , Receptores Citoplasmáticos e Nucleares/genética , Esteroide Hidroxilases/genética , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Sistemas CRISPR-Cas , Receptor Constitutivo de Androstano , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Família 2 do Citocromo P450/metabolismo , Feminino , Deleção de Genes , Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenômenos Farmacológicos e Toxicológicos , Receptores Citoplasmáticos e Nucleares/metabolismo , Esteroide Hidroxilases/metabolismo
14.
Pharmacol Ther ; 175: 47-66, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28223231

RESUMO

Drug discovery is a multidisciplinary and multivariate optimization endeavor. As such, in silico screening tools have gained considerable importance to archive, analyze and exploit the vast and ever-increasing amount of experimental data generated throughout the process. The current review will focus on the computer-aided prediction of the numerous properties that need to be controlled during the discovery of a preliminary hit and its promotion to a viable clinical candidate. It does not pretend to the almost impossible task of an exhaustive report but will highlight a few key points that need to be collectively addressed both by chemists and biologists to fuel the drug discovery pipeline with innovative and safe drug candidates.


Assuntos
Descoberta de Drogas , Simulação por Computador , Ensaios de Triagem em Larga Escala , Humanos , Farmacocinética , Fenômenos Farmacológicos e Toxicológicos
15.
Drug Discov Today Technol ; 20: 19-25, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27986219

RESUMO

Cerebral open flow microperfusion (cOFM) is a new in-vivo technique for continuous sampling of the interstitial fluid in brain tissue. cOFM can be used to monitor substance transport across the blood-brain barrier (pharmacokinetics) and to investigate metabolic changes in brain tissue after drug application (pharmacodynamics). The possibility of long-term implantation into the brain makes cOFM an outstanding tool in the development of brain relevant pharmaceutics.


Assuntos
Encéfalo/metabolismo , Perfusão/métodos , Animais , Microtecnologia/instrumentação , Microtecnologia/métodos , Perfusão/instrumentação , Farmacocinética , Fenômenos Farmacológicos e Toxicológicos
16.
Sci Rep ; 6: 30024, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27457921

RESUMO

The similarity of pair-wise diseases reveals the molecular relationships between them. For example, similar diseases have the potential to be treated by common therapeutic chemicals (TCs). In this paper, we introduced DisSim, an online system for exploring similar diseases, and comparing corresponding TCs. Currently, DisSim implemented five state-of-the-art methods to measure the similarity between Disease Ontology (DO) terms and provide the significance of the similarity score. Furthermore, DisSim integrated TCs of diseases from the Comparative Toxicogenomics Database (CTD), which can help to identify potential relationships between TCs and similar diseases. The system can be accessed from http://123.59.132.21:8080/DisSim.


Assuntos
Bases de Dados Factuais , Sistemas On-Line , Fenômenos Farmacológicos e Toxicológicos , Toxicogenética , Doença , Tratamento Farmacológico , Humanos
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