MultiDS-MDA: Integrating multiple data sources into heterogeneous network for predicting novel metabolite-drug associations.

Metabolic processes in the human body play an important role in maintaining normal life activities, and the abnormal concentration of metabolites is closely related to the occurrence and development of diseases. The use of drugs is considered to have a major impact on metabolism, and drug metabolites can contribute to efficacy, drug toxicity and drug-drug interaction. However, our understanding of metabolite-drug associations is far from complete, and individual data source tends to be incomplete and noisy. Therefore, the integration of various types of data sources for inferring reliable metabolite-drug associations is urgently needed. In this study, we proposed a computational framework, MultiDS-MDA, for identifying metabolite-drug associations by integrating multiple data sources, including chemical structure information of metabolites and drugs, the relationships of metabolite-gene, metabolite-disease, drug-gene and drug-disease, the data of gene ontology (GO) and disease ontology (DO) and known metabolite-drug connections. The performance of MultiDS-MDA was evaluated by 5-fold cross-validation, which achieved an area under the ROC curve (AUROC) of 0.911 and an area under the precision-recall curve (AUPRC) of 0.907. Additionally, MultiDS-MDA showed outstanding performance compared with similar approaches. Case studies for three metabolites (cholesterol, thromboxane B2 and coenzyme Q10) and three drugs (simvastatin, pravastatin and morphine) also demonstrated the reliability and efficiency of MultiDS-MDA, and it is anticipated that MultiDS-MDA will serve as a powerful tool for future exploration of metabolite-drug interactions and contribute to drug development and drug combination.

Computing Drug-Drug Similarity from Patient-Centric Data.

In modern biology and medicine, drug-drug similarity is a major task with various applications in pharmaceutical drug development. Various direct and indirect sources of evidence obtained from drug-centric data such as side effects, drug interactions, biological targets, and chemical structures are used in the current methods to measure the level of drug-drug similarity. This paper proposes a computational method to measure drug-drug similarity using a novel source of evidence that is obtained from patient-centric data. More specifically, patients' narration of their thoughts, opinions, and experience with drugs in social media are explored as a potential source to compute drug-drug similarity. Online healthcare communities were used to extract a dataset of patients' reviews on anti-epileptic drugs. The collected dataset is preprocessed through Natural Language Processing (NLP) techniques and four text similarity methods are applied to measure the similarities among them. The obtained similarities are then used to generate drug-drug similarity-based ranking matrices which are analyzed through Pearson correlation, to answer questions related to the overall drug-drug similarity and the accuracy of the four similarity measures. To evaluate the obtained drug-drug similarities, they are compared with the corresponding ground-truth similarities obtained from DrugSimDB, a well-known drug-drug similarity tool that is based on drug-centric data. The results provide evidence on the feasibility of patient-centric data from social media as a novel source for computing drug-drug similarity.

Analysis and identification of drug similarity through drug side effects and indications data.

BACKGROUND: The measurement of drug similarity has many potential applications for assessing drug therapy similarity, patient similarity, and the success of treatment modalities. To date, a family of computational methods has been employed to predict drug-drug similarity. Here, we announce a computational method for measuring drug-drug similarity based on drug indications and side effects. METHODS: The model was applied for 2997 drugs in the side effects category and 1437 drugs in the indications category. The corresponding binary vectors were built to determine the Drug-drug similarity for each drug. Various similarity measures were conducted to discover drug-drug similarity. RESULTS: Among the examined similarity methods, the Jaccard similarity measure was the best in overall performance results. In total, 5,521,272 potential drug pair's similarities were studied in this research. The offered model was able to predict 3,948,378 potential similarities. CONCLUSION: Based on these results, we propose the current method as a robust, simple, and quick approach to identifying drug similarity.

Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks.

Drug repositioning aims to discover novel clinical benefits of existing drugs, is an effective way to develop drugs for complex diseases such as cancer and may facilitate the process of traditional drug development. Meanwhile, network-based computational biology approaches, which allow the integration of information from different aspects to understand the relationships between biomolecules, has been successfully applied to drug repurposing. In this work, we developed a new strategy for network-based drug repositioning against cancer. Combining the mechanism of action and clinical efficacy of the drugs, a cancer-related drug similarity network was constructed, and the correlation score of each drug with a specific cancer was quantified. The top 5% of scoring drugs were reviewed for stability and druggable potential to identify potential repositionable drugs. Of the 11 potentially repurposable drugs for non-small cell lung cancer (NSCLC), 10 were confirmed by clinical trial articles and databases. The targets of these drugs were significantly enriched in cancer-related pathways and significantly associated with the prognosis of NSCLC. In light of the successful application of our approach to colorectal cancer as well, it provides an effective clue and valuable perspective for drug repurposing in cancer.

Deep learning in drug discovery: an integrative review and future challenges.

Recently, using artificial intelligence (AI) in drug discovery has received much attention since it significantly shortens the time and cost of developing new drugs. Deep learning (DL)-based approaches are increasingly being used in all stages of drug development as DL technology advances, and drug-related data grows. Therefore, this paper presents a systematic Literature review (SLR) that integrates the recent DL technologies and applications in drug discovery Including, drug-target interactions (DTIs), drug-drug similarity interactions (DDIs), drug sensitivity and responsiveness, and drug-side effect predictions. We present a review of more than 300 articles between 2000 and 2022. The benchmark data sets, the databases, and the evaluation measures are also presented. In addition, this paper provides an overview of how explainable AI (XAI) supports drug discovery problems. The drug dosing optimization and success stories are discussed as well. Finally, digital twining (DT) and open issues are suggested as future research challenges for drug discovery problems. Challenges to be addressed, future research directions are identified, and an extensive bibliography is also included.

Determining similarities of COVID-19 - lung cancer drugs and affinity binding mode analysis by graph neural network-based GEFA method.

COVID-19 is a worldwide health crisis seriously endangering the arsenal of antiviral and antibiotic drugs. It is urgent to find an effective antiviral drug against pandemic caused by the severe acute respiratory syndrome (Sars-Cov-2), which increases global health concerns. As it can be expensive and time-consuming to develop specific antiviral drugs, reuse of FDA-approved drugs that provide an opportunity to rapidly distribute effective therapeutics can allow to provide treatments with known preclinical, pharmacokinetic, pharmacodynamic and toxicity profiles that can quickly enter in clinical trials. In this study, using the structural information of molecules and proteins, a list of repurposed drug candidates was prepared again with the graph neural network-based GEFA model. The data set from the public databases DrugBank and PubChem were used for analysis. Using the Tanimoto/jaccard similarity analysis, a list of similar drugs was prepared by comparing the drugs used in the treatment of COVID-19 with the drugs used in the treatment of other diseases. The resultant drugs were compared with the drugs used in lung cancer and repurposed drugs were obtained again by calculating the binding strength between a drug and a target. The kinase inhibitors (erlotinib, lapatinib, vandetanib, pazopanib, cediranib, dasatinib, linifanib and tozasertib) obtained from the study can be used as an alternative for the treatment of COVID-19, as a combination of blocking agents (gefitinib, osimertinib, fedratinib, baricitinib, imatinib, sunitinib and ponatinib) such as ABL2, ABL1, EGFR, AAK1, FLT3 and JAK1, or antiviral therapies (ribavirin, ritonavir-lopinavir and remdesivir).Communicated by Ramaswamy H. Sarma.

Instruction of molecular structure similarity and scaffolds of drugs under investigation in ebola virus treatment by atom-pair and graph network: A combination of favipiravir and molnupiravir.

The virus that causes Ebola is fatal. Although many researchers have attempted to contain this deadly infection, the fatality rate remains high. The atom-pair fingerprint technique was used to compare drugs suggested for the treatment of Ebola or those that are currently being tested in clinical settings. Subsequently, using scaffold network graph (SNG) methods, the molecular and structural scaffolds of the drugs chosen based on these similar results were created, and the drug structures were examined. Public databases (PubChem and DrugBank) and literature regarding Ebola treatment were used in the analysis. Graphical representations of the molecular architecture and core structures of the drugs with the highest similarity to Food and Drug Administration (FDA)-approved drugs were produced using the SNG method. The combination of molnupiravir, the first licensed oral medication candidate for COVID-19, and favipiravir, employed in other viral outbreaks, should be further researched for treating Ebola, as observed in our study. We also believe that chemists will benefit from understanding the core structure(s) of medication molecules effective against the Ebola virus, their inhibitors, and the chemical structure similarities of existing pharmaceuticals utilized to build alternative drugs or drug combinations.

dialogi: Utilising NLP With Chemical and Disease Similarities to Drive the Identification of Drug-Induced Liver Injury Literature.

Drug-Induced Liver Injury (DILI), despite its low occurrence rate, can cause severe side effects or even lead to death. Thus, it is one of the leading causes for terminating the development of new, and restricting the use of already-circulating, drugs. Moreover, its multifactorial nature, combined with a clinical presentation that often mimics other liver diseases, complicate the identification of DILI-related (or "positive") literature, which remains the main medium for sourcing results from the clinical practice and experimental studies. This work-contributing to the "Literature AI for DILI Challenge" of the Critical Assessment of Massive Data Analysis (CAMDA) 2021- presents an automated pipeline for distinguishing between DILI-positive and negative publications. We used Natural Language Processing (NLP) to filter out the uninformative parts of a text, and identify and extract mentions of chemicals and diseases. We combined that information with small-molecule and disease embeddings, which are capable of capturing chemical and disease similarities, to improve classification performance. The former were directly sourced from the Chemical Checker (CC). For the latter, we collected data that encode different aspects of disease similarity from the National Library of Medicine's (NLM) Medical Subject Headings (MeSH) thesaurus and the Comparative Toxicogenomics Database (CTD). Following a similar procedure as the one used in the CC, vector representations for diseases were learnt and evaluated. Two Neural Network (NN) classifiers were developed: a baseline model that accepts texts as input and an augmented, extended, model that also utilises chemical and disease embeddings. We trained, validated, and tested the classifiers through a Nested Cross-Validation (NCV) scheme with 10 outer and 5 inner folds. During this, the baseline and extended models performed virtually identically, with F1-scores of 95.04 ± 0.61% and 94.80 ± 0.41%, respectively. Upon validation on an external, withheld, dataset that is meant to assess classifier generalisability, the extended model achieved an F1-score of 91.14 ± 1.62%, outperforming its baseline counterpart which received a lower score of 88.30 ± 2.44%. We make further comparisons between the classifiers and discuss future improvements and directions, including utilising chemical and disease embeddings for visualisation and exploratory analysis of the DILI-positive literature.

Does adding the drug-drug similarity to drug-target interaction prediction methods make a noticeable improvement in their efficiency?

Predicting drug-target interactions (DTIs) has become an important bioinformatics issue because it is one of the critical and preliminary stages of drug repositioning. Therefore, scientists are trying to develop more accurate computational methods for predicting drug-target interactions. These methods are usually based on machine learning or recommender systems and use biological and chemical information to improve the accuracy of predictions. In the background of these methods, there is a hypothesis that drugs with similar chemical structures have similar targets. So, the similarity between drugs as chemical information is added to the computational methods to improve the prediction results. The question that arises here is whether this claim is actually true? If so, what method should be used to calculate drug-drug chemical structure similarities? Will we obtain the same improvement from any DTI prediction method we use? Here, we investigated the amount of improvement that can be achieved by adding the drug-drug chemical structure similarities to the problem. For this purpose, we considered different types of real chemical similarities, random drug-drug similarities, four gold standard datasets and four state-of-the-art methods. Our results show that the type and size of data, the method which is used to predict the interactions, and the algorithm used to calculate the chemical similarities between drugs are all important, and it cannot be easily stated that adding drug-drug similarities can significantly improve the results. Therefore, our results could suggest a checklist for scientists who want to improve their machine learning methods.

A novel machine learning model based on sparse structure learning with adaptive graph regularization for predicting drug side effects.

Drug side effects are closely related to the success and failure of drug development. Here we present a novel machine learning method for side effect prediction. The proposed method treats side effect prediction as a multi-label learning problem and uses sparse structure learning to model the relationships between side effects. Additionally, the proposed method adopts the adaptive graph regularization strategy to explore the local structure in drug data and fuse multiple types of drug features. An alternating optimization algorithm is proposed to solve the optimization problem. We collected chemical structures and biological pathway features of drugs as the inputs of our method to predict drug side effects. The results of the cross-validation experiment showed that our method could significantly improve the prediction performance compared to the other state-of-the-art methods. Besides, our model is highly interpretable. It could learn the drug neighbourhood relationships, side effect relationships, and drug features related to side effects. We systematically validated the information extracted by the model with independent data. Some prediction results could also be supported by literature reports. The proposed method could be applied to integrate both chemical and biological data to predict side effects and helps improve drug safety.

A Method of Optimizing Weight Allocation in Data Integration Based on Q-Learning for Drug-Target Interaction Prediction.

Calculating and predicting drug-target interactions (DTIs) is a crucial step in the field of novel drug discovery. Nowadays, many models have improved the prediction performance of DTIs by fusing heterogeneous information, such as drug chemical structure and target protein sequence and so on. However, in the process of fusion, how to allocate the weight of heterogeneous information reasonably is a huge challenge. In this paper, we propose a model based on Q-learning algorithm and Neighborhood Regularized Logistic Matrix Factorization (QLNRLMF) to predict DTIs. First, we obtain three different drug-drug similarity matrices and three different target-target similarity matrices by using different similarity calculation methods based on heterogeneous data, including drug chemical structure, target protein sequence and drug-target interactions. Then, we initialize a set of weights for the drug-drug similarity matrices and target-target similarity matrices respectively, and optimize them through Q-learning algorithm. When the optimal weights are obtained, a new drug-drug similarity matrix and a new drug-drug similarity matrix are obtained by linear combination. Finally, the drug target interaction matrix, the new drug-drug similarity matrices and the target-target similarity matrices are used as inputs to the Neighborhood Regularized Logistic Matrix Factorization (NRLMF) model for DTIs. Compared with the existing six methods of NetLapRLS, BLM-NII, WNN-GIP, KBMF2K, CMF, and NRLMF, our proposed method has achieved better effect in the four benchmark datasets, including enzymes(E), nuclear receptors (NR), ion channels (IC) and G protein coupled receptors (GPCR).

Drug similarity and structure-based screening of medicinal compounds to target macrodomain-I from SARS-CoV-2 to rescue the host immune system: a molecular dynamics study.

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22, Ala38, Asn40, Val44, Phe144, Gly46, Gly47, Leu127, Ser128, Gly130, Ile131, Phe132 and Ala155 which are the critical active site residues. Here, we also used ADPr as a positive control to compare our results. Our results suggest that our identified hits by using such a complicated computational pipeline could inhibit the SARs-CoV-2 by targeting the macrodomain-1. We strongly recommend the experimental testing of these compounds, which could rescue the host immune system and could help to contain the disease caused by SARs-CoV-2.Communicated by Ramaswamy H. Sarma.

DrugSim2DR: systematic prediction of drug functional similarities in the context of specific disease for drug repurposing.

BACKGROUND: Traditional approaches to drug development are costly and involve high risks. The drug repurposing approach can be a valuable alternative to traditional approaches and has therefore received considerable attention in recent years. FINDINGS: Herein, we develop a previously undescribed computational approach, called DrugSim2DR, which uses a network diffusion algorithm to identify candidate anticancer drugs based on a drug functional similarity network. The innovation of the approach lies in the drug-drug functional similarity network constructed in a manner that implicitly links drugs through their common biological functions in the context of a specific disease state, as the similarity relationships based on general states (e.g., network proximity or Jaccard index of drug targets) ignore disease-specific molecular characteristics. The drug functional similarity network may provide a reference for prediction of drug combinations. We describe and validate the DrugSim2DR approach through analysis of data on breast cancer and lung cancer. DrugSim2DR identified some US Food and Drug Administration-approved anticancer drugs, as well as some candidate drugs validated by previous studies in the literature. Moreover, DrugSim2DR showed excellent predictive performance, as evidenced by receiver operating characteristic analysis and multiapproach comparisons in various cancer datasets. CONCLUSIONS: DrugSim2DR could accurately assess drug-drug functional similarity within a specific disease context and may more effectively prioritize disease candidate drugs. To increase the usability of our approach, we have developed an R-based software package, DrugSim2DR, which is freely available on CRAN (https://CRAN.R-project.org/package=DrugSim2DR).

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism.

The discovery of a drug requires over a decade of intensive research and financial investments - and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target COVID-19 and explains their inhibitory mechanism for further experimental screening. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.

Identification of 3D motifs based on sequences and structures for binding to CFI-400945, and deep screening-based design of new lead molecules for PLK-4.

PLK-4 kinase plays an essential role in the cell cycle from regulating centriole duplication till cytokinesis and is therefore an attractive drug target in cancers such as breast, lung, and central nervous system tumors. CFI-400945 is an efficient PLK-4 inhibitor and inhibits other non-PLK family proteins at nanomolar concentrations. We have compared PLK-4 with other kinases to understand its similarity based on multiple sequence alignments from protein sequences of primary structures, outer and buried residues, and compact active site conservation based on three-dimensional motifs. These in-depth studies provide information on known interface targets and design of more selective inhibitors to PLK-4. Further, pharmacophore features based on CFI-400945 bound to PLK-4 were used for searching library of compounds that were screened using deep learning methods to bind PLK-4. The shortlisted molecules were docked into PLK-4 active site and were validated using molecular docking and molecular dynamics simulations studies. MM-PBSA calculations revealed the stability of hit molecules and PLK-4 complexes in comparison with CFI-400945 and the contribution to binding from key active site residues.

SNF-NN: computational method to predict drug-disease interactions using similarity network fusion and neural networks.

BACKGROUND: Drug repositioning is an emerging approach in pharmaceutical research for identifying novel therapeutic potentials for approved drugs and discover therapies for untreated diseases. Due to its time and cost efficiency, drug repositioning plays an instrumental role in optimizing the drug development process compared to the traditional de novo drug discovery process. Advances in the genomics, together with the enormous growth of large-scale publicly available data and the availability of high-performance computing capabilities, have further motivated the development of computational drug repositioning approaches. More recently, the rise of machine learning techniques, together with the availability of powerful computers, has made the area of computational drug repositioning an area of intense activities. RESULTS: In this study, a novel framework SNF-NN based on deep learning is presented, where novel drug-disease interactions are predicted using drug-related similarity information, disease-related similarity information, and known drug-disease interactions. Heterogeneous similarity information related to drugs and disease is fed to the proposed framework in order to predict novel drug-disease interactions. SNF-NN uses similarity selection, similarity network fusion, and a highly tuned novel neural network model to predict new drug-disease interactions. The robustness of SNF-NN is evaluated by comparing its performance with nine baseline machine learning methods. The proposed framework outperforms all baseline methods ([Formula: see text] = 0.867, and [Formula: see text]=0.876) using stratified 10-fold cross-validation. To further demonstrate the reliability and robustness of SNF-NN, two datasets are used to fairly validate the proposed framework's performance against seven recent state-of-the-art methods for drug-disease interaction prediction. SNF-NN achieves remarkable performance in stratified 10-fold cross-validation with [Formula: see text] ranging from 0.879 to 0.931 and [Formula: see text] from 0.856 to 0.903. Moreover, the efficiency of SNF-NN is verified by validating predicted unknown drug-disease interactions against clinical trials and published studies. CONCLUSION: In conclusion, computational drug repositioning research can significantly benefit from integrating similarity measures in heterogeneous networks and deep learning models for predicting novel drug-disease interactions. The data and implementation of SNF-NN are available at http://pages.cpsc.ucalgary.ca/ tnjarada/snf-nn.php .

Drug-drug similarity measure and its applications.

Drug similarities play an important role in modern biology and medicine, as they help scientists gain deep insights into drugs' therapeutic mechanisms and conduct wet labs that may significantly improve the efficiency of drug research and development. Nowadays, a number of drug-related databases have been constructed, with which many methods have been developed for computing similarities between drugs for studying associations between drugs, human diseases, proteins (drug targets) and more. In this review, firstly, we briefly introduce the publicly available drug-related databases. Secondly, based on different drug features, interaction relationships and multimodal data, we summarize similarity calculation methods in details. Then, we discuss the applications of drug similarities in various biological and medical areas. Finally, we evaluate drug similarity calculation methods with common evaluation metrics to illustrate the important roles of drug similarity measures on different applications.

A comprehensive integrated drug similarity resource for in-silico drug repositioning and beyond.

Drug similarity studies are driven by the hypothesis that similar drugs should display similar therapeutic actions and thus can potentially treat a similar constellation of diseases. Drug-drug similarity has been derived by variety of direct and indirect sources of evidence and frequently shown high predictive power in discovering validated repositioning candidates as well as other in-silico drug development applications. Yet, existing resources either have limited coverage or rely on an individual source of evidence, overlooking the wealth and diversity of drug-related data sources. Hence, there has been an unmet need for a comprehensive resource integrating diverse drug-related information to derive multi-evidenced drug-drug similarities. We addressed this resource gap by compiling heterogenous information for an exhaustive set of small-molecule drugs (total of 10 367 in the current version) and systematically integrated multiple sources of evidence to derive a multi-modal drug-drug similarity network. The resulting database, 'DrugSimDB' currently includes 238 635 drug pairs with significant aggregated similarity, complemented with an interactive user-friendly web interface (http://vafaeelab.com/drugSimDB.html), which not only enables database ease of access, search, filtration and export, but also provides a variety of complementary information on queried drugs and interactions. The integration approach can flexibly incorporate further drug information into the similarity network, providing an easily extendable platform. The database compilation and construction source-code has been well-documented and semi-automated for any-time upgrade to account for new drugs and up-to-date drug information.

PIMD: An Integrative Approach for Drug Repositioning Using Multiple Characterization Fusion.

The accumulation of various types of drug informatics data and computational approaches for drug repositioning can accelerate pharmaceutical research and development. However, the integration of multi-dimensional drug data for precision repositioning remains a pressing challenge. Here, we propose a systematic framework named PIMD to predict drug therapeutic properties by integrating multi-dimensional data for drug repositioning. In PIMD, drug similarity networks (DSNs) based on chemical, pharmacological, and clinical data are fused into an integrated DSN (iDSN) composed of many clusters. Rather than simple fusion, PIMD offers a systematic way to annotate clusters. Unexpected drugs within clusters and drug pairs with a high iDSN similarity score are therefore identified to predict novel therapeutic uses. PIMD provides new insights into the universality, individuality, and complementarity of different drug properties by evaluating the contribution of each property data. To test the performance of PIMD, we use chemical, pharmacological, and clinical properties to generate an iDSN. Analyses of the contributions of each drug property indicate that this iDSN was driven by all data types and performs better than other DSNs. Within the top 20 recommended drug pairs, 7 drugs have been reported to be repurposed. The source code for PIMD is available at https://github.com/Sepstar/PIMD/.

Uncovering New Drug Properties in Target-Based Drug-Drug Similarity Networks.

Despite recent advances in bioinformatics, systems biology, and machine learning, the accurate prediction of drug properties remains an open problem. Indeed, because the biological environment is a complex system, the traditional approach-based on knowledge about the chemical structures-can not fully explain the nature of interactions between drugs and biological targets. Consequently, in this paper, we propose an unsupervised machine learning approach that uses the information we know about drug-target interactions to infer drug properties. To this end, we define drug similarity based on drug-target interactions and build a weighted Drug-Drug Similarity Network according to the drug-drug similarity relationships. Using an energy-model network layout, we generate drug communities associated with specific, dominant drug properties. DrugBank confirms the properties of 59.52% of the drugs in these communities, and 26.98% are existing drug repositioning hints we reconstruct with our DDSN approach. The remaining 13.49% of the drugs seem not to match the dominant pharmacologic property; thus, we consider them potential drug repurposing hints. The resources required to test all these repurposing hints are considerable. Therefore we introduce a mechanism of prioritization based on the betweenness/degree node centrality. Using betweenness/degree as an indicator of drug repurposing potential, we select Azelaic acid and Meprobamate as a possible antineoplastic and antifungal, respectively. Finally, we use a test procedure based on molecular docking to analyze Azelaic acid and Meprobamate's repurposing.