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Drug Discovery Today

M M Kanchi, M K Shanmugam, G Rane, G Sethi, A P Kumar
No abstract text is available yet for this article.
March 7, 2018: Drug Discovery Today
Sinisa Vukovic, David J Huggins
Ligandability is a prerequisite for druggability and is a much easier concept to understand, model and predict because it does not depend on the complex pharmacodynamic and pharmacokinetic mechanisms in the human body. In this review, we consider a metric for quantifying ligandability from experimental data. We discuss ligandability in terms of the balance between effort and reward. The metric is evaluated for a standard set of well-studied drug targets - some traditionally considered to be ligandable and some regarded as difficult...
March 6, 2018: Drug Discovery Today
Ola Engkvist, Per-Ola Norrby, Nidhal Selmi, Yu-Hong Lam, Zhengwei Peng, Edward C Sherer, Willi Amberg, Thomas Erhard, Lynette A Smyth
Over the past few decades, various computational methods have become increasingly important for discovering and developing novel drugs. Computational prediction of chemical reactions is a key part of an efficient drug discovery process. In this review, we discuss important parts of this field, with a focus on utilizing reaction data to build predictive models, the existing programs for synthesis prediction, and usage of quantum mechanics and molecular mechanics (QM/MM) to explore chemical reactions. We also outline potential future developments with an emphasis on pre-competitive collaboration opportunities...
March 3, 2018: Drug Discovery Today
Ricardo Garay, Carlos A Zarate, Icilio Cavero, Yong-Ku Kim, Thomas Charpeaud, Phil Skolnick
No abstract text is available yet for this article.
March 1, 2018: Drug Discovery Today
Tim K Mackey, John Annaloro
The withdrawal of the UK from the European Union (EU) is a complicated event. Although implications vary by industry, the biotechnology sector is especially vulnerable to the consequences of Brexit. Accordingly, here we evaluate potential repercussions under four post-Brexit political pathways: European Economic Area (EEA) affiliation (Norwegian Model); (negotiated bilateral access (Swiss Model); limited participation in EU Customs Union (Turkish Model); or independence under the World Trade Organization (WTO) designation...
March 1, 2018: Drug Discovery Today
Ping-Pin Zheng, Johan M Kros, Jin Li
Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta™ for the treatment of adult patients with R/R large B cell lymphoma. In common, both drugs are CD19-specific CAR T cell therapies lysing CD19-positive targets. Their dramatic efficacy in the short term has been highlighted by many media reports...
March 1, 2018: Drug Discovery Today
Bhuvaneshwar Vaidya, Ali Ehsan Sifat, Vardan T Karamyan, Thomas J Abbruscato
Novel neuroprotective therapies are desperately needed to improve neuronal recovery after ischemic stroke and extend the therapeutic window or offset some of the adverse effects of tissue-type plasminogen activator (tPA). These advances could provide a more effective and safe therapeutic regimen for patients with ischemic stroke. The opioid system has gained intense interest over the past fw years and is currently being investigated as a viable target for the pharmacological treatment of stroke. In this review, we focus on different opioid receptors (ORs) and their distribution in the central nervous system (CNS), and the effect of ischemic stroke on their redistribution...
March 1, 2018: Drug Discovery Today
Lulu Cai, Zhipeng Gu, Jian Zhong, Di Wen, Guojun Chen, Lin He, Jun Wu, Zhen Gu
To enhance efficacy and safety, therapeutic antitumor agents are expected to target the desired locations where the ligand-receptor binding acts as a typical recognition approach. Among the various ligands, carbohydrates represent a crucial structure of tumor cell membranes and have been shown effective for cell-selective drug delivery. Recently, glycosylation-mediated therapeutic targeting strategies have been increasingly developed to form a variety of nanoscale delivery carriers. In this review, a variety of glycosylated drug delivery systems and their applications for cancer therapy have been surveyed...
February 28, 2018: Drug Discovery Today
Diana Santos-Ribeiro, Laurent Godinas, Charles Pilette, Frédéric Perros
The integrated stress response system represents an ancillary, extremely conserved signalling pathway present in virtually all eukaryotic cells, which plays an important part in the pathophysiology of several disorders such as cancer and neurodegeneration. However, its role in the cardiovascular system remains largely elusive. Hence, this review aims to acknowledge recent findings regarding the action of the eIF2α kinases in the cardiovascular system and their role in the pathophysiology of related disorders...
February 27, 2018: Drug Discovery Today
Mohammad Norouzi
Despite much effort to treat glioblastoma multiforme (GBM), the median survival of patients has not significantly improved. The high rate of tumor recurrence after tumor resection and the blood-brain barrier (BBB) decrease treatment efficacy. Local drug delivery at the surgical resection site via implantable electrospun nanofibers not only circumvents the BBB, but can also reduce the rate of tumor recurrence. Nanofibers can provide the sustained release and high concentration of chemotherapeutics at the tumor vicinity, while decreasing their systemic exposure and toxicity...
February 27, 2018: Drug Discovery Today
Ankit Saneja, Robin Kumar, Divya Arora, Sandeep Kumar, Amulya K Panda, Sundeep Jaglan
In recent years, research has focused on the development of smart nanocarriers that can respond to specific stimuli. Among the various stimuli-responsive platforms for cancer therapy, near-infrared (NIR) light (700-1000nm)-responsive nanocarriers have gained considerable interest because of their deeper tissue penetration capacity, precisely controlled drug release, and minimal damage towards normal tissues. In this review, we outline various therapeutic applications of NIR-responsive nanocarriers in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), and bioimaging...
February 23, 2018: Drug Discovery Today
Yvonne Schuller, Maarten Arends, Simon Körver, Mirjam Langeveld, Carla E M Hollak
Fabry disease (FD) is a rare X-chromosome-linked lysosomal storage disorder. Although initial expectations of enzyme replacement therapy (ERT) were high, it is now clear that real-world effectiveness is disappointing and evidence gathering has been inadequate. In retrospect, development of ERT for FD had several shortcomings. Little convincing evidence on the effectiveness existed at time of authorization. Also, post-marketing evaluation failed to generate sufficient and relevant data for adequate evaluation on effectiveness...
February 15, 2018: Drug Discovery Today
Mahadevabharath R Somayaji, Debarun Das, Andrzej J Przekwas
No abstract text is available yet for this article.
February 8, 2018: Drug Discovery Today
Miryam Mebarki, Annelise Bennaceur, Laurence Bonhomme-Faivre
In oncology, a 2D in vitro model of cancer cell lines is still widely used for large-scale drug screening. However, most promising candidates firstly identified by in vitro analysis tend to fail during the next steps of drug development. The generation of an ex vivo approach termed 'organoid' is emerging as a promising preclinical model to mimic human tumors more accurately. In this review, we focus on human-derived organoid use for anticancer drug screening. We describe the development of this new in vitro model, its use for anticancer agent assays and the advantages compared with the currently used 2D models...
February 8, 2018: Drug Discovery Today
Rajendran J C Bose, Ramasamy Paulmurugan, James Moon, Soo-Hong Lee, Hansoo Park
Cancer is a leading cause of death worldwide. The use of nanocarriers (NCs) has generated significant interest to improve cancer therapy by targeted delivery. However, conventional NCs in general lack specificity and have poor biodistribution, resulting in low efficacy in cancer therapy. To circumvent this problem, there has been an increasing focus on cancer cell membrane-coated NCs (CCMCNCs), which can deliver therapeutics directly to tumor cells. CCMCNCs comprise active cancer cell surface adhesive molecules combined with other functional proteins, and offer extended blood circulation with robust cell-specific targeting, ensuring enhanced intratumoral penetration and higher tumor-specific accumulation of NCs...
February 6, 2018: Drug Discovery Today
Yeong L Tan, Han K Ho
The existing and exploratory drug delivery routes for albumin-based nanoparticles are collectively summarised in this review.
February 3, 2018: Drug Discovery Today
Edward O'Neill, Guleid Awale, Leila Daneshmandi, Obum Umerah, Kevin W-H Lo
Bone scientists are actively investigating a range of methods to promote skeletal tissue regeneration. A review of recent literature has revealed that several ions are uniquely capable of inducing stem cell differentiation down desired lineages. There exists enormous promise for these ions to be used in bone regenerative medicine. Given that these ions can be released from biodegradable polymeric materials, their long-term delivery can be achieved through a variety of controlled-release strategies compared with the relatively few options available for expensive and fragile polypeptide-based growth factors...
February 3, 2018: Drug Discovery Today
Manickam Yogavel, Rini Chaturvedi, Palak Babbar, Nipun Malhotra, Vitul Jain, Amit Sharma
Malaria remains a major infectious disease and, despite incidence reduction, it threatens resurgence in drug-resistant forms. Antimalarial drugs remain the mainstay of therapeutic options and hence there is a constant need to identify and validate new druggable targets. Plasmodium falciparum aminoacyl-tRNA synthetases (Pf-aaRSs) drive protein translation and are potent targets for development of next-generation antimalarials. Here, we detail advances made in structural-biology-based investigations in Pf-aaRSs and discuss their distribution of druggable pockets...
February 2, 2018: Drug Discovery Today
Chao Chen
Clinical proof-of-concept trials crucially inform major resource deployment decisions. This paper discusses several mechanisms for enhancing their rigour and efficiency. The importance of careful consideration when using a surrogate endpoint is illustrated; situational effectiveness of run-in patient enrichment is explored; a versatile tool is introduced to ensure a high probability of pharmacological success; the benefits of dose-titration are revealed by simulation; and the importance of adequately scheduled observations is shown...
January 31, 2018: Drug Discovery Today
Vibhuti Agrahari, Vivek Agrahari
There are numerous hurdles hindering the clinical translation of nanomedicines. The major challenges are: reproducible manufacturing and scale-up, availability of appropriate characterization methods, instability under in vivo environments, safety issues, poor understanding of the disease heterogeneity and patient preselection strategies, regulatory barriers and inadequate understanding of the biophysical and chemical interactions of nanoformulations. Technologies such as quality-by-design, process analytical techniques and microfluidics could significantly accelerate the translation of nanomedicines...
January 31, 2018: Drug Discovery Today
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