Journal Cover
Drug Discovery Today
Journal Prestige (SJR): 2.008
Citation Impact (citeScore): 6
Number of Followers: 171  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 1359-6446
Published by Elsevier Homepage  [3182 journals]
  • A human-on-a-chip approach to tackling rare diseases
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Camilly P. Pires de Mello, John Rumsey, Victoria Slaughter, James J. HickmanDrug development for rare diseases, classified as diseases with a prevalence of < 200 000 patients, is limited by the high cost of research and low target population. Owing to a lack of representative disease models, research has been challenging for orphan drugs. Human-on-a-chip (HoaC) technology, which models human tissues in interconnected in vitro microfluidic devices, has the potential to lower the cost of preclinical studies and increase the rate of drug approval by introducing human phenotypic models early in the drug discovery process. Advances in HoaC technology can drive a new approach to rare disease research and orphan drug development.
       
  • Pharmacological analysis of CFTR variants of cystic fibrosis using stem
           cell-derived organoids
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Kevin G. Chen, Pingyu Zhong, Wei Zheng, Jeffrey M. BeekmanCystic fibrosis (CF) is a life-shortening genetic disease caused by mutations of CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator. Despite considerable progress in CF therapies, targeting specific CFTR genotypes based on small molecules has been hindered because of the substantial genetic heterogeneity of CFTR mutations in patients with CF, which is difficult to assess by animal models in vivo. There are broadly four classes (e.g., II, III, and IV) of CF genotypes that differentially respond to current CF drugs (e.g., VX-770 and VX-809). In this review, we shed light on the pharmacogenomics of diverse CFTR mutations and the emerging role of stem cell-based organoids in predicting the CF drug response. We discuss mechanisms that underlie differential CF drug responses both in organoid-based assays and in CF clinical trials, thereby facilitating the precision design of safer and more effective therapies for individual patients with CF.Graphical abstractGraphical abstract for this article
       
  • CDx, NGS and regulation: five perspectives from the Pistoia Alliance
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): John Wise, Mike Furness, Stewart McWilliams, Simon PattonCompanion diagnostics (CDx) are essential to the practice of precision medicine. Next-generation sequencing is an increasingly important tool in the development of CDx. However, for CDx to be deployed, many different biopharma industry sectors need to collaborate. This paper outlines some of the challenges and opportunities perceived by the biopharmaceutical industry, the Europe Molecular Quality Network, a regulatory agency, a notified body and a CDx service provider.
       
  • Regulatory sanctions for ethically relevant GCP violations
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Rosemarie de la Cruz Bernabe, Ghislaine J.M.W. van Thiel, Nancy S. Breekveldt, Christine C. Gispen, Johannes J.M. van DeldenAlthough EU inspectors and clinical assessors are mandated to identify and act upon ethical issues, regulators lack guidance on how this can be done. Hence, we propose a four-step regulatory approach on ethically relevant GCP violation findings. The first step is identification of the ethical issue. Next is analysis [i.e., identifying the gravity (intensity or severity) and the magnitude (amount and duration) of the ethics violation as well as the responsible person(s) or entity or entities]. The third step is evaluation, (i.e., the process of deliberating to determine the significance of the ethics violation, with the intention of identifying the most reasonable sanction and/or corrective or reparative action). Last is decision-making or the process of choosing and implementing a regulatory course of action.
       
  • Target 2035: probing the human proteome
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Adrian J. Carter, Oliver Kraemer, Matthias Zwick, Anke Mueller-Fahrnow, Cheryl H. Arrowsmith, Aled M. EdwardsBiomedical scientists tend to focus on only a small fraction of the proteins encoded by the human genome despite overwhelming genetic evidence that many understudied proteins are important for human disease. One of the best ways to interrogate the function of a protein and to determine its relevance as a drug target is by using a pharmacological modulator, such as a chemical probe or an antibody. If these tools were available for most human proteins, it should be possible to translate the tremendous advances in genomics into a greater understanding of human health and disease, and catalyze the creation of innovative new medicines. Target 2035 is a global federation for developing and applying new technologies with the goal of creating chemogenomic libraries, chemical probes, and/or functional antibodies for the entire proteome.
       
  • The Art of Virtualizing Pharma R&D
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Alexander Schuhmacher, Oliver Gassmann, Michael Kuss, Markus Hinder
       
  • Contents page 2
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s):
       
  • Contents page 1
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s):
       
  • Animal venoms: therapeutic tools for tackling Parkinson’s disease
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Henrique de Oliveira Amaral, Victoria Monge-Fuentes, Andréia Biolchi Mayer, Gabriel Avohay Alves Campos, Kamila Soares Lopes, Luana C. Camargo, Matheus Ferroni Schwartz, Priscilla Galante, Márcia R. MortariParkinson’s disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation. With long-term use, conventional treatments can become inefficient, often triggering possible side effects. Considering these drawbacks, drug discovery constantly turns to nature as a source of efficient therapeutics. Thus, this review explores animal venoms as a rich source of bioactive compounds with potent neuropharmacological profiles for the development of effective adjuvant treatments with fewer side effects, ultimately aiming for the neuroprotection of dopaminergic neurons and the symptomatic relief of PD.
       
  • Targeted cell delivery for articular cartilage regeneration and
           osteoarthritis treatment
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Nahid Nasiri, Samaneh Hosseini, Mauro Alini, Ali Khademhosseini, Mohamadreza Baghaban EslaminejadOsteoarthritis (OA) is one of the main causes of pain and disability worldwide. In recent years, numerous efforts have been made in pharmaceutical and surgical therapies for OA management. The therapeutic features of mesenchymal stem cells (MSCs), have led to numerous preclinical and clinical trials that confirmed the efficacy of cell therapy as treatment for OA. Recent works have attempted to customize cell participation in tissue regeneration using site specific targeting approaches. Targeting approaches are based on direct modifications to the surface of MSCs or indirect modifications on an engineered nanomediator. Here, we provide a comprehensive review of the advances in targeted cell delivery and define the priorities for future work in terms of OA and cartilage regeneration.
       
  • PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a
           review on drug discovery and future challenges
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Mohammad A. Khan, Vineet K. Jain, Md. Rizwanullah, Javed Ahmad, Keerti JainTriple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer associated with poor prognosis. Although conventional chemotherapy regimens have shown some effectiveness in early TNBC cases, the outcome in advanced stages is poor. The PI3K/AKT/mTOR pathway is one of the important and active pathways involved in chemoresistance and survival of TNBC. This pathway is speculated to play an important part in malignant transformation and has been considered as a potential molecular target for the design of therapeutic agents to treat TNBC. This review discusses the potentials and drug discovery perspectives of PI3K/AKT/mTOR as a therapeutic target for effective management of TNBC with anticipated challenges.
       
  • Novel insights into the role of urotensin II in cardiovascular disease
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): João Pereira-Castro, Carmen Brás-Silva, Ana Patrícia Fontes-SousaUrotensin II (UII) is a vasoactive peptide that interacts with a specific receptor called the UT receptor. UII has been implicated in cardiovascular regulation, with promising therapeutic applications based on UT receptor antagonism. The endogenous ligands of the UT receptor: UII and urotensin-related peptide (URP), differentially bind and activate this receptor. Also, the receptor localization is not restricted to the plasma membrane, possibly inducing different physiological responses that could support its inconsistent, but potent, vasoactive activity. These properties could explain the disappointing outcomes in clinical studies, in contrast to the positive preclinical results regarding heart failure, pulmonary hypertension, atherosclerosis and diabetes mellitus. These aspects should be considered in future investigations to a better comprehension of the role of UII as a potential therapeutic target.
       
  • Nuclear G-protein-coupled receptors as putative novel pharmacological
           targets
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Rita Ribeiro-Oliveira, Martin Vojtek, Salomé Gonçalves-Monteiro, Maria Sofia Vieira-Rocha, Joana B. Sousa, Jorge Gonçalves, Carmen DinizCell surface G-protein-coupled receptors (GPCRs) are targets for ∼ 30% of drugs currently on the market, and are the largest group of gene products targeted by drugs. Until recently, signaling mediated by GPCRs was thought to emanate exclusively from the cell membrane as a response to extracellular stimuli. However, recent research has revealed the existence of nuclear (n)GPCRs with the ability to trigger identical and/or distinct signaling pathways to their respective counterparts on the cell surface. Understanding of the GPCR signaling platform on the nuclear membranes and its involvement in physiology and/or pathophysiology will be important to develop selective pharmacological and pharmaceutical approaches. In this review, we summarize our current understanding of nGPCRs, with emphasis on their potential as novel pharmacological targets.
       
  • Pharmaceutical applications of cyclotides
    • Abstract: Publication date: November 2019Source: Drug Discovery Today, Volume 24, Issue 11Author(s): Paola G. Ojeda, Marlon H. Cardoso, Octávio L. FrancoCyclotides are cyclic peptides, present in several plant families, that show diverse biological properties. Structurally, cyclotides share a distinctive head-to-tail circular knotted topology of three disulfide bonds. This framework provides cyclotides with extraordinary resistance to thermal and chemical denaturation. There is increasing interest in the therapeutic potential of cyclotides, which combine several promising pharmaceutical properties, including binding affinity, target selectivity, and low toxicity towards healthy mammalian cells. Recently, cyclotides have been reported to be orally bioavailable and have proved to be amenable to modifications. Here, we provide an overview of the structure, properties, and pharmaceutical applications of cyclotides.
       
  • Epigenetic role of thymoquinone: impact on cellular mechanism and cancer
           therapeutics
    • Abstract: Publication date: Available online 18 September 2019Source: Drug Discovery TodayAuthor(s): Md. Asaduzzaman Khan, Mousumi Tania, Junjiang FuThymoquinone is a natural product known for its anticancer activity. Preclinical studies indicated numerous mechanisms of action by which thymoquinone exerts its effects on cancer cells. Recent evidence has indicated that thymoquinone can modulate epigenetic machinery, like modifying histone acetylation and deacetylation, DNA methylation and demethylation, which are among the major epigenetic changes that can contribute to carcinogenesis. Moreover, thymoquinone can alter the genetic expression of various noncoding RNAs, such as miRNA and lncRNA, which are the key parts of cellular epigenetics. This review focuses on cellular epigenetic systems, epigenetic changes responsible for cancer and the counteraction of thymoquinone to target epigenetic challenges, which might be among the mechanisms of the thymoquinone effect in cancer cells.
       
  • Allosteric inhibition of HIF-2α as a novel therapy for clear cell
           renal cell carcinoma
    • Abstract: Publication date: Available online 18 September 2019Source: Drug Discovery TodayAuthor(s): Yancheng Yu, Quanwei Yu, Xiaojin ZhangClear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC and bears a significantly high frequency of hypoxia-inducible factor 2α (HIF-2α) because of von Hippel-Lindau (VHL) tumor suppressor gene mutations. From the first discovery of HIF-2α inhibitors to the promising potency of the HIF-2α inhibitor PT2977 in a clinical Phase II trial for the treatment of advanced RCC, inhibition of HIF-2α has proved to be a novel and effective therapy for RCC. In this review, we briefly discuss the role of HIF-2α in ccRCC and provide insight into recent advances in the discovery, development, and mode of action of HIF-2α allosteric inhibitors.Graphical abstractGraphical abstract for this article
       
  • Activity-based proteomic profiling: application of releasable linker in
           photoaffinity probes
    • Abstract: Publication date: Available online 7 November 2019Source: Drug Discovery TodayAuthor(s): Jin Wang, Qinhua Chen, Yuanyuan Shan, Xiaoyan Pan, Jie ZhangCombining releasable chemical crosslinkers with photoaffinity probes represents a valuable tool for identifying protein–protein interactions (PPIs). The biomacromolecule photoaffinity probe prepared by using releasable photoaffinity linkers can be used to exploring PPIs by triggering release of the releasable group. More importantly, it can overcome the shortcomings of macromolecular photoaffinity probes without label transfer functionality to accurately confirm defects in specific structural sites. It shows particular promise for research exploring the interaction of unknown proteins and transient–weak PPIs in living organisms to discover new drug targets. In this review, we highlight recent progress in the development and application of chemical releasable linkers in photoaffinity probes. Several comparative studies are described in which the efficiency of various photoaffinity probes are compared.
       
  • Enhancing the potential preclinical and clinical benefits of quercetin
           through novel drug delivery systems
    • Abstract: Publication date: Available online 7 November 2019Source: Drug Discovery TodayAuthor(s): Rubiya Khursheed, Sachin Kumar Singh, Sheetu Wadhwa, Monica Gulati, Ankit AwasthiQuercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the development of various diseases. Despite its proven therapeutic potential, the clinical use of quercetin remains limited because of its low aqueous solubility, bioavailability, and substantial first-pass metabolism. To overcome this, several novel formulations have been reported. In this review, we focus on the applications of quercetin extract as well as its novel formulations for treating different disorders. We also examine its proposed mechanism of action of quercetin.
       
  • A drug-likeness toolbox facilitates ADMET study in drug discovery
    • Abstract: Publication date: Available online 6 November 2019Source: Drug Discovery TodayAuthor(s): Chen-Yang Jia, Jing-Yi Li, Ge-Fei Hao, Guang-Fu YangUndesirable pharmacokinetic (PK) properties or unacceptable toxicity are the main causes of the failure of drug candidates at the clinical trial stage. Since the concept of drug-likeness was first proposed, it has become an important consideration in the selection of compounds with desirable bioavailability during the early phases of drug discovery. Over the past decade, online resources have effectively facilitated drug-likeness studies in an economical and time-efficient manner. Here, we provide a comprehensive summary and comparison of current accessible online resources, in terms of their key features, application fields, and performance for in silico drug-likeness studies. We hope that the assembled toolbox will provide useful guidance to facilitate future in silico drug-likeness research.Graphical abstractGraphical abstract for this article
       
  • Nonclinical data supporting orphan medicinal product designations in the
           area of rare infectious diseases
    • Abstract: Publication date: Available online 5 November 2019Source: Drug Discovery TodayAuthor(s): Maria E. Sheean, Eva Malikova, Dinah Duarte, Giuseppe Capovilla, Laura Fregonese, Matthias Hofer, Armando Magrelli, Segundo Mariz, Fernando Mendez-Hermida, Robert Nistico, Tim Leest, Nikolaos V. Sipsas, Stelios Tsigkos, Dinko Vitezic, Kristina Larsson, Bruno Sepodes, Violeta Stoyanova-BeninskaThe Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) is responsible for evaluating applications for orphan designation (OMPDs) and for deciding the orphan status at the time of marketing authorization of medicines in the European Union (EU). In this review, we provide transparency regarding assessment criteria and an in-depth review of nonclinical models and data that have been used to support OMPDs. Additionally, we present a literature-based analysis of existing nonclinical models and discuss key features of nonclinical studies, which are considered crucial for the support of future OMPDs. This could not only inform future drug development in rare infectious conditions, but also indicate areas where nonclinical models are indispensable or can be made more efficient.
       
  • LMWH and its derivatives represent new rational for cancer therapy:
           construction strategies and combination therapy
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Shi Du, Yao Yu, Cheng Xu, Hui Xiong, Shan Yang, Jing YaoLow-molecular-weight heparin (LMWH) has attracted increasing attention as a tumor treatment because of its board range of physiological functions. Over the past decade, diverse LMWH derivatives have increased the variety of antitumor strategies available, serving not only as anti-tumor agents, but also as drug delivery platforms. In this review, we introduce the basic strategy for structural modification of LMWH to attenuate its antitumor activity while reducing its risk of bleeding and immune responses, as well as highlighting current applications of LMWH and its derivatives in cancer therapy. We select representative drug delivery systems involving LMWH derivatives and discuss the construction principles and therapeutic effects associated with their use. We also analyze progress made in the development of antitumor combination therapies, in which LMWH has shown synergistic or combined effects with other treatment strategies.
       
  • Ontology mapping for semantically enabled applications
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Ian Harrow, Rama Balakrishnan, Ernesto Jimenez-Ruiz, Simon Jupp, Jane Lomax, Jane Reed, Martin Romacker, Christian Senger, Andrea Splendiani, Jabe Wilson, Peter WoollardIn this review, we provide a summary of recent progress in ontology mapping (OM) at a crucial time when biomedical research is under a deluge of an increasing amount and variety of data. This is particularly important for realising the full potential of semantically enabled or enriched applications and for meaningful insights, such as drug discovery, using machine-learning technologies. We discuss challenges and solutions for better ontology mappings, as well as how to select ontologies before their application. In addition, we describe tools and algorithms for ontology mapping, including evaluation of tool capability and quality of mappings. Finally, we outline the requirements for an ontology mapping service (OMS) and the progress being made towards implementation of such sustainable services.
       
  • Exosomal miRNA in chemoresistance, immune evasion, metastasis and
           progression of cancer
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Bhagyashri Kulkarni, Prathibha Kirave, Piyush Gondaliya, Kavya Jash, Alok Jain, Rakesh K. Tekade, Kiran KaliaIn the treatment of cancer, there are three significant limitations causing high mortality and recurrence rates among cancer patients. First, the escape of tumor cells from the immune system; second, the development of multi‐drug resistance (MDR) to chemotherapeutic drugs; and, third, the noxious metastases of cancer cells. Exosomes are vesicular cargos involved in the transportation of miRNA, mRNA and proteins from one cell to another cell. This review details the current understanding of the exosomal transmission of miRNA and crosstalk with the downstream consequences, ultimately leading to the progression and metastasis of cancer. Further, this review also discusses how exosomal miRNA can provide promising novel targets for the treatment and detection of cancer.
       
  • Cervical cancer and HPV infection: ongoing therapeutic research to
           counteract the action of E6 and E7 oncoproteins
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Ana M. Almeida, João A. Queiroz, Fani Sousa, Ângela SousaCervical cancer is the fourth most common cancer among women worldwide and its development is mainly associated with human papillomavirus infection, a highly sexually transmissible virus. The expression of E6 and E7 viral oncoproteins deregulates cell repairing mechanisms through impairment of tumor suppressor protein functions, such as p53 or retinoblastoma protein. Although the implementation of new preventive vaccines has decreased the infection rate and cervical cancer progression, there are still many women who are affected by this pathology. Nowadays, the main treatment often requires the use of invasive techniques. From well-established strategies, like DNA vaccines and gene therapy, to innovative gene silencing technologies; different methodologies are currently under scrutiny that target the E6 and E7 oncoproteins and/or their modes of action.
       
  • Contents page 1
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s):
       
  • Contents page 2
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s):
       
  • Sharpening the focus on cancer tumours
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Josephine Bunch
       
  • Drug repurposing: a promising tool to accelerate the drug discovery
           process
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Vineela Parvathaneni, Nishant S. Kulkarni, Aaron Muth, Vivek GuptaTraditional drug discovery and development involves several stages for the discovery of a new drug and to obtain marketing approval. It is necessary to discover new strategies for reducing the drug discovery time frame. Today, drug repurposing has gained importance in identifying new therapeutic uses for already-available drugs. Typically, repurposing can be achieved serendipitously (unintentional fortunate observations) or through systematic approaches. Numerous strategies to discover new indications for FDA-approved drugs are discussed in this article. Drug repurposing has therefore become a productive approach for drug discovery because it provides a novel way to explore old drugs for new use but encounters several challenges. Some examples of different approaches are reviewed here.
       
  • Are we ready to close the discussion on the interchangeability of
           biosimilars'
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Hans C. Ebbers, Huub SchellekensSince the introduction of the first biosimilar the discussion about their interchangeability has persisted. The body of evidence gathered for biosimilars provides reassurance that they are approved based on a rigorous comparability exercise and do not show clinically meaningful differences to their reference products. There are no data suggesting that the risk of switching to a biosimilar in terms of increased immunogenicity is greater than switching between two batches of any biologic. The key concern around switching biosimilars is the nocebo effect, which reinforces the need for physician involvement when switching. Whereas this might argue against automatic substitution of biosimilars, it is not a biosimilars-specific concern. To increase physician confidence in biosimilars, regulators should acknowledge that biosimilars are interchangeable.
       
  • Neurobiology and therapeutic utility of neurotoxins targeting postsynaptic
           mechanisms of neuromuscular transmission
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Naira M. Ayvazyan, Valerie B. O’Leary, J. Oliver Dolly, Saak V. OvsepianThe neuromuscular junction (NMJ) is the principal site for the translation of motor neurochemical signals to muscle activity. Therefore, the release and sensing machinery of acetylcholine (ACh) along with muscle contraction are two of the main targets of natural toxins and pathogens, causing paralysis. Given pharmacology and medical advances, the active ingredients of toxins that target postsynaptic mechanisms have become of major interest, showing promise as drug leads. Herein, we review key facets of prevalent toxins modulating the mechanisms of ACh sensing and generation of the postsynaptic response, with muscle contraction. We consider the correlation between their outstanding selectivity and potency plus effects on motor function, and discuss emerging data advocating their usage for the development of therapies alleviating neuromuscular dysfunction.
       
  • Nucleolin-based targeting strategies for cancer therapy: from targeted
           drug delivery to cytotoxic ligands
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Sofia Romano, Nuno Fonseca, Sérgio Simões, João Gonçalves, João Nuno MoreiraCancer is currently the second leading cause of death worldwide and current therapeutic approaches remain ineffective in several cases. Therefore, there is a need to develop more efficacious therapeutic agents, especially for subtypes of cancer lacking targeted therapies. Limited drug penetration into tumors impairs the efficacy of therapies targeting cancer cells. One of the strategies to overcome this problem is targeting the more accessible tumor vasculature via molecules such as nucleolin, which is expressed at the surface of cancer and angiogenic endothelial cells, thus enabling a dual cellular targeting strategy. In this review, we present and discuss nucleolin-based targeting strategies that have been developed for cancer therapy, with a special focus on recent antibody-based approaches.
       
  • Revisiting mTOR inhibitors as anticancer agents
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Qiu-Xu Teng, Yunali V. Ashar, Pranav Gupta, Eddie Gadee, Ying-Fang Fan, Sandra E. Reznik, John N.D. Wurpel, Zhe-Sheng ChenThe mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates a variety of cellular processes, influencing diverse pathological conditions including a variety of cancers. Accordingly, therapies that target mTOR as anticancer agents benefit patients in various clinical settings. It is therefore important to fully investigate mTOR signaling at a molecular level and corresponding mTOR inhibitors to identify additional clinical opportunities of targeting mTOR in cancers. In this review, we introduce the function and regulation of the mTOR signaling pathway and organize and summarize the different roles of mTOR in cancers and a variety of mTOR inhibitors that can be used as anticancer agents. This article aims to enlighten and guide the development of mTOR-targeted anticancer agents in the future.
       
  • Methods to identify and optimize small molecules interacting with RNA
           (SMIRNAs)
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Andrei Ursu, Simon Vézina-Dawod, Matthew D. DisneyRNAs, particularly noncoding RNAs (ncRNAs), are becoming increasingly important therapeutic targets, because they are causative and antagonists of human disease. Indeed, aberrant RNA structural elements and expression deregulate biological processes. In this review, we describe methodologies to discover and optimize small molecules interacting with RNA (SMIRNAs), including the evaluation of direct target engagement and the rescue of RNA-mediated phenotypes in vitro and in vivo. Such studies are essential to fully characterize the mode of action of SMIRNAs and advance our understanding of rationally and efficiently drugging RNAs for therapeutic benefit.
       
  • Deep learning in drug discovery: opportunities, challenges and future
           prospects
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Antonio LavecchiaArtificial Intelligence (AI) is an area of computer science that simulates the structures and operating principles of the human brain. Machine learning (ML) belongs to the area of AI and endeavors to develop models from exposure to training data. Deep Learning (DL) is another subset of AI, where models represent geometric transformations over many different layers. This technology has shown tremendous potential in areas such as computer vision, speech recognition and natural language processing. More recently, DL has also been successfully applied in drug discovery. Here, I analyze several relevant DL applications and case studies, providing a detailed view of the current state-of-the-art in drug discovery and highlighting not only the problematic issues, but also the successes and opportunities for further advances.
       
  • The influence of ketamine on drug discovery in depression
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Christoph Kraus, Daniel Wasserman, Ioline D. Henter, Elia Acevedo-Diaz, Bashkim Kadriu, Carlos A. ZarateRecent research demonstrating that the glutamatergic modulator ketamine has rapid, robust, and sustained antidepressant effects has been a turning point in drug discovery for depression. The recent FDA approval of esketamine for adults with treatment-resistant major depressive disorder (MDD) has further underscored the relevance of this agent in spurring investigation into novel and mechanistically distinct agents for use in depression. Over the past two decades, ketamine research has ushered in a new wave of studies seeking to not only identify its mechanism of action but also to examine the antidepressant potential of novel or repurposed agents. This article reviews the approaches that have proven particularly fruitful for the field of neuropsychiatry.
       
  • Potential effects of increased openness in pharma: the original knowledge
           behind new drugs
    • Abstract: Publication date: October 2019Source: Drug Discovery Today, Volume 24, Issue 10Author(s): Francesca Bignami, Pauline MattssonThis study seeks to determine potential changes in the degree of openness in pharmaceutical R&D by investigating where the knowledge behind new molecular entities (NMEs) comes from in terms of type of organization, geography and time. We find that the organizations granted NMEs increasingly rely on external knowledge sources but that these are increasingly shared among NME grantees. Universities are the most important indirect knowledge contributor and their relative importance has increased with time. NME grantees are increasingly relying on knowledge from different countries and the age of the knowledge sources confirms that recent NMEs are mostly follow-on drugs. This work provides evidence of the increasing openness of pharma to new knowledge sources as a means to improving the drug discovery and development process.
       
  • Introducing Project Africa GRADIENT
    • Abstract: Publication date: Available online 4 November 2019Source: Drug Discovery TodayAuthor(s): Iris Rajman, Oscar Della Pasqua, on behalf of the Joint Steering Committee Africa GRADIENT
       
  • A Special Exception for CBD in Foods and Supplements'
    • Abstract: Publication date: Available online 3 November 2019Source: Drug Discovery TodayAuthor(s): Patricia J. Zettler, Erika Lietzan
       
  • Changing biotechnology dynamics – A blessing or a curse'
    • Abstract: Publication date: Available online 1 November 2019Source: Drug Discovery TodayAuthor(s): Merve Memisoglu
       
  • Drug-induced liver injury severity and toxicity (DILIst): binary
           classification of 1303 drugs by human hepatotoxicity
    • Abstract: Publication date: Available online 1 November 2019Source: Drug Discovery TodayAuthor(s): Shraddha Thakkar, Ting Li, Zhichao Liu, Leihong Wu, Ruth Roberts, Weida TongDrug-induced liver injury (DILI) is of significant concern to drug development and review because of the limited success with existing preclinical models. For developing alternative methods, a large drug list is needed with known DILI severity and toxicity. We augmented the DILIrank data set [annotated using US Food and Drug Administration (FDA) drug labeling)] with four literature datasets (N>350 drugs) to generate the largest drug list with DILI classification, called DILIst (DILI severity and toxicity). DILIst comprises 1303 drugs, of which 789 a DILI positives (increase of 69% from DILIrank), whereas 514 were DILI negatives (increase of 66%). The investigation of DILI positive–negative distribution across various therapeutic categories revealed the most and least frequent DILI categories. Thus, we consider DILIst to be an invaluable resource for the community to improve DILI research.Graphical abstractGraphical abstract for this article
       
  • Drugs, discovery, and dermatology: Renbök, research and repurposing
    • Abstract: Publication date: Available online 31 October 2019Source: Drug Discovery TodayAuthor(s): Sidharth Sonthalia, Mahima Agrawal, Virendra N. Sehgal, Vijay Gandhi, Kripa S. Gupta
       
  • Synthetic Biology – Reimagine Drug Discovery
    • Abstract: Publication date: Available online 31 October 2019Source: Drug Discovery TodayAuthor(s): Stephanie Brooking
       
  • Decoy oligodeoxynucleotide technology: an emerging paradigm for breast
           cancer treatment
    • Abstract: Publication date: Available online 25 October 2019Source: Drug Discovery TodayAuthor(s): Maryam Mahjoubin Tehran, Samaneh Rezaei, Amin Jalili, Seyed Hamid Aghaee-Bakhtiari, Amirhossein SahebkarBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, which is resistant to conventional therapies. Therefore, there is an urgent need to identify new therapies for treating incurable breast cancer in patients. Decoy oligodeoxynucleotides (ODNs) are synthetic oligonucleotides that have a high affinity for a specific transcription factor and can be transfected into target cells to bind to their respective target and alter gene transcription. With these powerful tools available, it is highly possible to effectively regulate the expression of genes that are involved in the pathogenesis of breast cancer. Here, we highlight the studies using decoy ODNs for the development of novel therapies against breast cancer.
       
  • Trapping endothelin-1 to hunt down cardiovascular disease'
    • Abstract: Publication date: Available online 22 October 2019Source: Drug Discovery TodayAuthor(s): Bernhard Wernly, Christian Jung
       
  • Emergence of allosteric drug-resistance mutations: new challenges for
           allosteric drug discovery
    • Abstract: Publication date: Available online 18 October 2019Source: Drug Discovery TodayAuthor(s): Shaoyong Lu, Yuran Qiu, Duan Ni, Xinheng He, Jun Pu, Jian ZhangAllosteric drugs have several significant advantages over traditional orthosteric drugs, encompassing higher selectivity and lower toxicity. Although allosteric drugs have potential advantages as therapeutic agents to treat human diseases, allosteric drug-resistance mutations still occur, rendering these drugs ineffective. Here, we review the emergence of allosteric drug-resistance mutations with an emphasis on examples covering clinically important therapeutic targets, including Breakpoint cluster region-Abelson tyrosine kinase (Bcr-Abl), Akt kinase [also called Protein Kinase B (PKB)], isocitrate dehydrogenase (IDH), MAPK/ERK kinase (MEK), and SRC homology 2 domain-containing phosphatase 2 (SHP2). We also discuss challenges associated with tackling allosteric drug resistance and the possible strategies to overcome this issue.
       
  • Nose-to-brain delivery of antiglioblastoma drugs embedded into lipid
           nanocarrier systems: status quo and outlook
    • Abstract: Publication date: Available online 17 October 2019Source: Drug Discovery TodayAuthor(s): Fakhara Sabir, Ruba Ismail, Ildiko CsokaGlioblastoma (GBM) is one of the most devastating and deadly types of tumor. Among all the present treatment strategies, the utmost prerequisite is prolonged intervention at the malignant site. The blood–brain barrier (BBB) is the bottleneck in the delivery of anti-GBM drugs and invasive treatment comes with many pitfalls. This review will discuss the potential of embedding antitumor drugs into nanocarriers for intranasal delivery. Additionally, it emphasizes the significance of applying quality by design (QbD) methodology from the early development stages to ensure the high quality, safety and efficacy of the developed carrier system.Graphical abstractGraphical abstract for this article
       
  • Horses for courses: an approach to the qualification of clinical trial
           sites and investigators in ATMPs
    • Abstract: Publication date: Available online 16 October 2019Source: Drug Discovery TodayAuthor(s): Martin HildebrandtThe advanced therapy medicinal products (ATMPs) landscape is entirely different from classical drug development. Academia has been the major source of ATMP development, and academic hospitals act as trial sites for the clinical testing of ATMPs, including early academic-led trials as well as industry-sponsored trials that pursue the full developmental pathway to market authorization. The recent breakthrough developments in some ATMPs, such as genetically engineered immune cells, have confronted academic hospitals with a substantial amount of public demand, competitive pressure, and costs. At the same time, risks, toxicities, and necessary countermeasures demand an infrastructure, and expertise and training have not yet been fully standardized. How can Ethics Committees consider trial sites and investigators in clinical trials with ATMPs as appropriately qualified'
       
  • Regulating membrane lipid levels at the synapse by small-molecule
           inhibitors of monoacylglycerol lipase: new developments in therapeutic and
           PET imaging applications
    • Abstract: Publication date: Available online 14 October 2019Source: Drug Discovery TodayAuthor(s): Natasha L. Grimsey, Juha R. Savinainen, Bala Attili, Muneer AhamedEndocannabinoid degrading enzymes regulate the concentrations of a variety of biomolecules, many of which are consequential in clinical pathologies. Monoacylglycerol lipase (MAGL) is the major enzyme involved in endocannabinoid (2-AG) hydrolysis. There is considerable interest in exploiting the therapeutic potential of MAGL in several central nervous system (CNS) disorders. The versatility, sensitivity and quantitative nature of positron emission tomography (PET) makes it ideal for functional imaging of the living brain at a molecular level. Consequently, there have been several approaches reported to develop PET ligands for imaging MAGL. This review provides an overview of the pharmacological role of MAGL in CNS disorders and a comprehensive account of development and application of MAGL inhibitors in imaging and therapy.
       
  • Heterogeneous surface-modified nanoplatforms for the targeted therapy of
           haematological malignancies
    • Abstract: Publication date: Available online 12 October 2019Source: Drug Discovery TodayAuthor(s): Sanjay Kulkarni, Abhijeet Pandey, Srinivas MutalikHere, we focus on nanoparticle (NP)-based platforms for the targeted therapy of haematological malignancies (HMs), providing an overview of surface-modified nanoplatforms, such as aptamer-, metal-, nucleic acid-, toxin, and peptide-modified NPs, for the efficient targeting of tumor cells. We discuss NPs targeting subcellular compartments, including mitochondria, nucleus and Golgi apparatus, for enhanced therapy of HMs. We also review stimuli-responsive nanoplatforms for modulating site-specific release of drugs. We provide insight into alternative modes of therapy, such as phototherapy, gene therapy, dendritic cell (DC) therapy, and radiotherapy, highlighting recent advances in the treatment of HMs.Graphical abstractGraphical abstract for this article
       
  • Site-specific bioconjugation and self-assembly technologies for
           multi-functional biologics: on the road to the clinic
    • Abstract: Publication date: Available online 11 October 2019Source: Drug Discovery TodayAuthor(s): Sung In LimThe expanding portfolio of biotherapeutics both in the research and development (R&D) and market sectors is shaping new opportunities towards multifunctional biologics (MFBs). The combination of new or pre-existing therapeutic agents into a single multifunctional format makes it possible to develop new pharmacological actions to significantly improve their efficacy and safety. In this review, I focus on novel platform technologies that are being exploited in the biotech industry to produce MFBs with potential therapeutic benefits that include half-life extension, targeted delivery, T cell engagement, and improved vaccination. In this regard, technologies of key importance are site-specific bioconjugation and self-assembly, which allow homogeneous, defined, and scalable process developments for several MFBs that are advancing towards clinical applications.
       
  • Physicochemical properties affecting the fate of nanoparticles in
           pulmonary drug delivery
    • Abstract: Publication date: Available online 7 October 2019Source: Drug Discovery TodayAuthor(s): Qiaoyu Liu, Jian Guan, Lu Qin, Xin Zhang, Shirui MaoThe inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles after deposition in the lung. First, physiological structure and characteristics of the lung are described. Thereafter, physicochemical properties that could influence the clearance and translocation of nanoparticles in the lung are discussed, including particle size, surface charge and surface hydrophilicity. It is believed that, with a better understanding of the fate of nanoparticles in the lung, it will broaden their application in inhalation for a better therapeutic effect in the future.Graphical abstractGraphical abstract for this article
       
  • Chemometrics: a complementary tool to guide the isolation of
           pharmacologically active natural products
    • Abstract: Publication date: Available online 7 October 2019Source: Drug Discovery TodayAuthor(s): Axhell A. Cornejo-Báez, Luis M. Peña-Rodríguez, Radames Alvarez-Zapata, Maribel Vazquez-Hernández, Alberto Sánchez-MedinaNatural products (NPs) are specialized metabolites from natural sources, such as plants, animals, fungi, and bacteria, that have had an important role in the discovery and development of new drugs. For many years, bioassay-guided isolation has been the most used strategy for the isolation of bioactive NPs. Chemometrics is the science of relating the measurements made in a system or chemical process to the application of mathematical and statistical methods. Recently, chemometric techniques have been widely used in NP studies, including the detection of bioactive NPs from medicinal plants, chemotaxonomy, determination of geographical origin of medicinal plants and herbal products, and for quality control purposes. In this review, we propose a chemometric-enhanced strategy as a new approach for speeding up the isolation of bioactive NPs while reducing the quantities of biological material and organic solvents used.
       
  • Ionic liquids: green and tailor-made solvents in drug delivery
    • Abstract: Publication date: Available online 5 October 2019Source: Drug Discovery TodayAuthor(s): Weizi Huang, Xiying Wu, Jianping Qi, Quangang Zhu, Wei Wu, Yi Lu, Zhongjian ChenBeyond their traditional use as green solvents, new applications have become available for ionic liquids (ILs) in drug delivery. Their flexible tunability enables task-specific optimization of ILs at molecular level. Thus, ILs have been exploited to improve the solubility and permeability of drugs and relieve the polymorphic problems associated with crystalline active pharmaceutical ingredients (APIs). Controlled preparation of drug nanocarriers are also achieved by using ILs either as media or as functional agents. Here, we highlight the importance and advantages of ILs in pharmaceutics and look towards the future of IL-based drug delivery.Graphical abstractGraphical abstract for this article
       
  • Clinical applications of nanomedicine in cancer therapy
    • Abstract: Publication date: Available online 3 October 2019Source: Drug Discovery TodayAuthor(s): Mohammad Norouzi, Mehrnaz Amerian, Mahshid Amerian, Fatemeh AtyabiCancer incidence and mortality are rapidly growing worldwide. In attempts to develop more efficacious therapeutic regimens for patients with cancer, nanomedicines have found increasing applications. Findings reveal that nanomedicines improve the clinical outcomes of cancer treatment by virtue of modified pharmacokinetics (PK) and biodistributions of the bioactive agents while reducing their systemic toxicity and adverse effects. Here, we provide an update on cancer nanomedicines that have been clinically approved and paradigmatic nanomedicines utilized in various therapeutic platforms undergoing Phase II/III clinical trials. We discuss the role of the developed nanomedicines in the improvement of current therapeutic regimens from both therapeutic and PK standpoints. By describing the state-of-the-art of nanomedicine and discussing their clinical advantages and challenges, we provide a perspective on the development of more effective therapeutic regimens to improve the clinical outcomes of cancer treatments.Graphical abstractGraphical abstract for this article
       
  • Iron oxide nanoparticles for therapeutic applications
    • Abstract: Publication date: Available online 3 October 2019Source: Drug Discovery TodayAuthor(s): Edouard AlphandéryIn nanomedicine, iron oxide nanoparticles are at an advanced stage, being commercialized for cancer treatment and iron-deficiency anemia treatment. Their therapeutic efficacy comes from their ability to target a tissue, activate a drug, locally produce reactive oxygen species or a temperature increase following (or not) the application of an external source of energy, modify genes or activate various biological materials, or replace diseased cells by stem cells. Owing to these various mechanisms of action, they can potentially be used for treating a whole range of different diseases, making them more appealing than conventional drugs that target a more limited number of indications.
       
  • Can BDDCS illuminate targets in drug design'
    • Abstract: Publication date: Available online 1 October 2019Source: Drug Discovery TodayAuthor(s): Giovanni Bocci, Leslie Z. Benet, Tudor I. OpreaThe fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we show that certain protein families have a clear preference for drugs with specific PK properties. We investigate this by cross-referencing ‘druggable target’ annotations for>1000 US Food and Drug Administration (FDA)-approved drugs with their PK profile, as defined by the Biopharmaceutics Drug Disposition Classification System (BDDCS) criteria, and then examine the BDDCS preference for several major target protein families and therapeutic categories. Our findings suggest a novel way to conduct drug discovery by focusing PK profiles at the very early stage of target selection.
       
  • The NCATS Pharmaceutical Collection: a 10-year update
    • Abstract: Publication date: Available online 1 October 2019Source: Drug Discovery TodayAuthor(s): Ruili Huang, Hu Zhu, Paul Shinn, Deborah Ngan, Lin Ye, Ashish Thakur, Gurmit Grewal, Tongan Zhao, Noel Southall, Mathew D. Hall, Anton Simeonov, Christopher P. AustinThe National Center for Advancing Translational Sciences (NCATS) Pharmaceutical Collection (NPC), a comprehensive collection of clinically approved drugs, was made a public resource in 2011. Over the past decade, the NPC has been systematically profiled for activity across an array of pathways and disease models, generating an unparalleled amount of data. These data have not only enabled the identification of new repurposing candidates with several in clinical trials, but also uncovered new biological insights into drug targets and disease mechanisms. This retrospective provides an update on the NPC in terms of both successes and lessons learned. We also report our efforts in bringing the NPC up-to-date with drugs approved in recent years.
       
  • Target discovery using biobanks and human genetics
    • Abstract: Publication date: Available online 25 September 2019Source: Drug Discovery TodayAuthor(s): Michael A. Hicks, Claire Y.C. Hou, Arya Iranmehr, Krisztina Marosi, Ewen KirknessLarge-scale biobanks can yield unprecedented insights into our health and provide discoveries of new and potentially targetable biomarkers. Several protective loss-of-function alleles have been identified, including variants that protect against cardiovascular disease, obesity, type 2 diabetes, and asthma and allergic diseases. These alleles serve as indicators of efficacy, mimicking the effects of drugs and suggesting that inhibiting these genes could provide therapeutic benefit, as has been observed for PCSK9. We provide a context for these findings through a multifaceted review covering the use of genetics in drug discovery efforts through genome-wide and phenome-wide association studies, linking deep mutation scanning data to molecular function and highlighting some additional tools that might help in the interpretation of newly discovered variants.Graphical abstractGraphical abstract for this article
       
  • Mind the gap! A survey of the challenges of biomarker commercialization
    • Abstract: Publication date: Available online 25 September 2019Source: Drug Discovery TodayAuthor(s): Susan Raths, Sven Parkel, Jesper Bredmose, Valérie Daussin‘Mind the gap!’ refers to both the gap between the identification and validation of biomarkers and the gap in knowledge between the stakeholder groups, where the researchers who discover the biomarkers often have little knowledge about the commercialization process. This gap is addressed here in a survey with relevant stakeholders conducted by the project ‘Biomarker Commercialization’ (BIC).
       
  • Dual-peptide ligand masks: a proposed treatment approach to stop prion
           disease dementias
    • Abstract: Publication date: Available online 24 September 2019Source: Drug Discovery TodayAuthor(s): Kevin RoePrion disease dementias are currently not treatable practically. However, a proposed treatment approach using specifically targeted dual-peptide ligand masks can mask prion surface proteins and treat specific prion diseases. Different approaches might be used to treat these prion diseases. One treatment introduces genetically modified cells into the gastrointestinal tract or other locations to produce dual-peptide ligand masks; and another treatment introduces only the dual-peptide ligand masks into the center of prion infections to mask prion surface proteins. An independent group introduced genetically modified therapeutic bacteria into large numbers of mammals, including several human volunteers, with safe and effective experimental results, without long-term colonization by the bacteria, which experimentally supports the feasibility of the first treatment. These approaches offer several advantages compared with theoretical treatments against prion diseases in humans.
       
  • Reaching for the bright StARs in chemical space
    • Abstract: Publication date: Available online 23 September 2019Source: Drug Discovery TodayAuthor(s): José L. Medina-Franco, J. Jesús Naveja, Edgar López-LópezdVisualization of activity data in chemical space is common in drug discovery. Navigating the space in a systematic manner is not trivial, given its size and huge coverage. To this end, methods for data visualization have been developed charting biological activity into chemical space. Herein, we review the progress in different visualization approaches to explore the chemical space aiming at reaching insightful structure–activity relationships (SARs) in the chemical space. We discuss recent methods including consensus diversity plots, ChemMaps, and constellation plots. Several of the methods we review can be extended to analyze other properties of interest in medicinal chemistry, such as structure–toxicity relationships, and can be adapted to postprocess results of virtual screening (VS) of large compound libraries.
       
  • The importance of target binding kinetics for measuring target binding
           affinity in drug discovery: a case study from a CRF1 receptor antagonist
           program
    • Abstract: Publication date: Available online 23 September 2019Source: Drug Discovery TodayAuthor(s): Sam R.J. Hoare, Beth A. Fleck, John P. Williams, Dimitri E. GrigoriadisIn drug discovery, it is essential to accurately measure drug–target binding affinity. Here, we revisit the fact that target binding kinetics impact the measurement of affinity, using a case study: development of corticotropin-releasing factor antagonists. Slow dissociation of the drug–target complex results in affinity assays being far from equilibrium, which results in erroneous estimates of affinity. This scenario impairs prediction of human dosing, assessment of target selectivity, identification of high-affinity ligands and determination of SAR. We describe strategies to detect lack of equilibration in affinity assays and methods to correctly measure affinity of slowly dissociating compounds. These considerations will facilitate drug discovery by ensuring reliable measurement of drug–target binding affinity.Graphical abstractGraphical abstract for this article
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
Home (Search)
Subjects A-Z
Publishers A-Z
Customise
APIs
Your IP address: 34.231.21.123
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-