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An update on the role of nanovehicles in nose-to-brain drug delivery.
Abstract A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, it is difficult for them to outperform conventional formulations, such as solutions or gels. However, nanovehicles bring about special features, such as maintenance of the solubilized state of drugs, sustained or delayed release, and enhanced penetration because of surface modifications, all ...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Feng Y, He H, Li F, Lu Y, Qi J, Wu W Tags: Drug Discov Today Source Type: research

Using network-based expert engagement to advance pharmaceutical research and development.
PMID: 29330121 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Ashkenazy R Tags: Drug Discov Today Source Type: research

Privileged portal metastasis of hepatocellular carcinoma in light of the coevolution of a visceral portal system and liver in the chordate lineage: a search for therapeutic targets.
Abstract Hepatocellular carcinoma (HCC) disseminates systemically, but metastases occur in distant organs in only a few patients, whereas HCC routinely metastasizes to liver and its vessels. HCC cells disseminate via hepatic veins, but portal veins are affected by metastasis more frequently than are hepatic veins, and correlates with poor prognosis. In this review, I suggest that privileged HCC portal metastasis occurs because of high levels of pancreatic family hormones and growth factors (PHGFs) in the portal blood. The analysis suggests that the appearance of the portal system carrying PHGFs in the evolution of...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Subbotin VM Tags: Drug Discov Today Source Type: research

A bibliometric review of drug repurposing.
Abstract We have conducted a bibliometric review of drug repurposing by scanning>25 million papers in PubMed and using text-mining methods to gather, count and analyze chemical-disease therapeutic relationships. We find that>60% of the ∼35 000 drugs or drug candidates identified in our study have been tried in more than one disease, including 189 drugs that have been tried in>300 diseases each. Whereas in the majority of cases these drugs were applied in therapeutic areas close to their original use, there have been striking, and perhaps instructive, successful attempts of drug repurposing for unexpec...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Baker NC, Ekins S, Williams AJ, Tropsha A Tags: Drug Discov Today Source Type: research

Manipulating the epigenome for the treatment of disorders with thrombotic complications.
Abstract The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications. Targeting these epigenetic changes could provide a new avenue for the treatment of pathological blood clots. However, the lack of tissue specificity warrants high-resolution ...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Kwa FAA, Jackson DE Tags: Drug Discov Today Source Type: research

The hitchhiker's guide to the chemical-biological galaxy.
tti A Abstract We are used to considering chemical and biological spaces as two different entities; although they represent a more-interconnected world, in fact they represent a Yin-Yang concept in drug discovery. Chemical-biological space is as vast as the universe and, as Douglas Adams famously said, 'Space is big. You just won't believe how vastly, hugely, mind-bogglingly big it is'. However, many researchers are convinced that it is not so infinite, and are designing computational and experimental tools to help identify and explore all possible chemical-biological space. Here, we provide an analysis of their a...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Opassi G, Gesù A, Massarotti A Tags: Drug Discov Today Source Type: research

Recent progress in the discovery of myeloid differentiation 2 (MD2) modulators for inflammatory diseases.
Abstract Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4 (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A domain of LPS, leading to the activation of downstream signaling of cytokine and chemokine production, and initiation of inflammatory and immune responses. However, excessive activation and potent host responses generate severe inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly being considered as an attractive pharmacological target for the de...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Chen L, Fu W, Zheng L, Wang Y, Liang G Tags: Drug Discov Today Source Type: research

Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: how far can they be simplified?
Abstract During the past decade, decreasing the attrition rate of drug development candidates reaching the market has become one of the major challenges in pharmaceutical research and drug development (R&D). To facilitate the decision-making process, and to increase the probability of rapidly finding and developing high-quality compounds, a variety of multiparametric guidelines, also known as rules and ligand efficiency (LE) metrics, have been developed. However, what are the 'best' descriptors and how far can we simplify these drug-likeness prediction tools in terms of the numerous, complex properties that th...
Source: Drug Discovery Today - January 9, 2018 Category: Drugs & Pharmacology Authors: Mignani S, Rodrigues J, Tomas H, Jalal R, Singh PP, Majoral JP, Vishwakarma RA Tags: Drug Discov Today Source Type: research

Overcoming the resistance mechanisms of Smoothened inhibitors.
Abstract Smoothened (Smo), the main transducer of the Hedgehog (Hh) signaling pathway, is a promising target for anticancer therapy. Although vismodegib and sonidegib have demonstrated effectiveness for the treatment of basal cell carcinoma (BCC), their clinical use has been associated with mutation-related drug resistance. In this review, we outline the resistance mechanisms of Smo inhibitors and point the way for future endeavors. We focus in particular on the development of second-generation Smo inhibitors based on co-crystal structures, inhibition of downstream components, and the regulation of other interacti...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Dong X, Wang C, Chen Z, Zhao W Tags: Drug Discov Today Source Type: research

Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery.
Abstract Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9 (CRISPR/Cas9) enables targeted genome engineering. The simplicity of this system, its facile engineering, and amenability to multiplex genes make it the system of choice for many applications. This system has revolutionized our ability to carry out gene editing, transcription regulation, genome imaging, and epigenetic modification. In this review, we discuss the discovery of CRISPR/Cas9, its mechanism of action, its application in medicine and animal model development, and its delivery. We also highlight how the CRISPR/Cas9 syste...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Ahmad G, Amiji M Tags: Drug Discov Today Source Type: research

Phage-derived lysins as potential agents for eradicating biofilms and persisters.
Abstract Bacterial biofilms are highly resistant to the action of antibiotics. Presence of persisters, phenotypically resistant populations of bacterial cells, is thought to contribute toward recalcitrance of biofilms. The phage-derived lysins, by virtue of their ability to cleave the peptidoglycan of bacterial cells in an enzymatic manner, have the unique ability to kill dormant cells. Several lysins have shown potent antibiofilm activity in vitro. The fact that lysins have shown better efficacy than conventional drugs in animal models of endocarditis and other infections involving biofilms suggests that the lysi...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Sharma U, Vipra A, Channabasappa S Tags: Drug Discov Today Source Type: research

Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement?
Abstract A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead® carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the Complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals. Based on overwhelming evidence of a role of anaphylatoxins in hypersensitivity rea...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Szebeni J Tags: Drug Discov Today Source Type: research

NCp7: targeting a multitask protein for next-generation anti-HIV drug development part 2. Noncovalent inhibitors and nucleic acid binders.
Abstract Nucleocapsid protein 7 (NCp7) represents a viable target not yet reached by the currently available antiretrovirals. It is a small and highly basic protein, which is essential for multiple stages of the viral replicative cycle, with its structure preserved in all viral strains, including clinical isolates. NCp7 can be inhibited covalently, noncovalently and by shielding the nucleic acid (NA) substrates of its chaperone activity. Although covalent NCp7 inhibitors have already been detailed in the first part of this review series, the focus here is based on noncovalent and NA-binder inhibitors and on the an...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Iraci N, Tabarrini O, Santi C, Sancineto L Tags: Drug Discov Today Source Type: research

Unlocking the full potential of open innovation in the life sciences through a classification system.
Abstract A common understanding of expectations and requirements is critical for boosting research-driven business opportunities in open innovation (OI) settings. Transparent communication requires common definitions and standards for OI to align the expectations of both parties. Here, we suggest a five-level classification system for OI models, reflecting the degree of openness. The aim of this classification system is to reduce contract negotiation complexity and times between two parties looking to engage in OI. Systematizing definitions and contractual terms for OI in the life sciences helps to reduce entry ba...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Nilsson N, Minssen T Tags: Drug Discov Today Source Type: research

Light-triggerable formulations for the intracellular controlled release of biomolecules.
Abstract New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-ba...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Lino MM, Ferreira L Tags: Drug Discov Today Source Type: research

Macromolecule nanotherapeutics: approaches and challenges.
Abstract With the advent of technology, newer forms of drugs, such as proteins, DNA, and RNA, have entered mainstream product development. However, systemic delivery of macromolecules is limited by rapid blood clearance, poor stability in vivo, and inadequate uptake by cells. Nanoparticle (NP)-based delivery systems have emerged as suitable carriers for overcoming such pharmacokinetic limitations of macromolecule delivery. Nanocarriers, such as liposomes, provide protection for sensitive drug materials and also enhance the circulation half-life of=therapeutics. Nanocarriers have also been shown to promote cellular...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Tyagi P, Santos JL Tags: Drug Discov Today Source Type: research

Pharmaceutical nanocrystals: production by wet milling and applications.
Abstract Nanocrystals are regarded as an important nanoformulation approach exhibiting advantages of increased dissolution and saturation solubility with chemical stability and low toxicity. Nanocrystals are produced in the form of nanosuspensions using top-down (e.g., wet milling or high pressure homogenization) and bottom-up methods (e.g., antisolvent precipitation). Wet milling is a scalable method applicable to drugs with different physicochemical and mechanical properties. Nanocrystalline-based formulations, either as liquid nanosuspensions or after downstream processing to solid dosage forms, have been devel...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Malamatari M, Taylor KMG, Malamataris S, Douroumis D, Kachrimanis K Tags: Drug Discov Today Source Type: research

Ligandomics: a paradigm shift in biological drug discovery.
Abstract As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adve...
Source: Drug Discovery Today - January 8, 2018 Category: Drugs & Pharmacology Authors: Li W, Pang IH, Pacheco MTF, Tian H Tags: Drug Discov Today Source Type: research

Astrocytes as targets for drug discovery.
Abstract Recent studies have illuminated the crucial role of astrocytes in maintaining proper neuronal health and function. Abnormalities in astrocytic functions have now been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Historically, drug development programs for neurodegenerative diseases generally target only neurons, overlooking the contributions of astrocytes. Therefore, targeting both disease neurons and astrocytes offers a new approach for drug development for th...
Source: Drug Discovery Today - January 6, 2018 Category: Drugs & Pharmacology Authors: Gorshkov K, Aguisanda F, Thorne N, Zheng W Tags: Drug Discov Today Source Type: research

From clinical proof-of-concept to commercialization of CAR T cells.
Abstract The development of CAR T cells currently represents an exciting opportunity to convert the already published clinical successes observed in clinical trials into commercially available efficient therapies. However, the path toward successful commercialization is still hindered by many hurdles. Here, we review such issues as: the need for structured collaborations between hospital collection and clinical facilities and industry manufacturing facilities to streamline the supply chain; necessity for uniform and efficient medical procedures to cope with severe toxicities associated with CAR T cells; and absolu...
Source: Drug Discovery Today - January 6, 2018 Category: Drugs & Pharmacology Authors: Calmels B, Mfarrej B, Chabannon C Tags: Drug Discov Today Source Type: research

The microRNA landscape of cutaneous squamous cell carcinoma.
ova Z Abstract Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for>20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is>1000000 cases per year, of which roughly 20-30% are squamous cell carcinoma. To better understand and treat this challenging cancer, current research focuses on development of novel strategies to improve the understanding of tumor biogenesis on an individual basis. microRNAs are becoming important biomarkers in the diagn...
Source: Drug Discovery Today - January 6, 2018 Category: Drugs & Pharmacology Authors: Konicke K, Lopez A, Muñoz JL, Servin LS, Flores A, Olasz E, Lazarova Z Tags: Drug Discov Today Source Type: research

Administration of antioxidants in cancer: debate of the decade.
Abstract Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal mod...
Source: Drug Discovery Today - January 6, 2018 Category: Drugs & Pharmacology Authors: Khurana RK, Jain A, Jain A, Sharma T, Singh B, Kesharwani P Tags: Drug Discov Today Source Type: research

Corrigendum to "Bispecific antibodies" [Drug Discov. Today 20 (July (7)) (2015) 838-847].
Corrigendum to "Bispecific antibodies" [Drug Discov. Today 20 (July (7)) (2015) 838-847]. Drug Discov Today. 2018 Jan 05;: Authors: Kontermann RE, Brinkmann U PMID: 29309739 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - January 5, 2018 Category: Drugs & Pharmacology Authors: Kontermann RE, Brinkmann U Tags: Drug Discov Today Source Type: research

Corrigendum to "Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal" [Drug Discov. Today 22 (February (2)) (2017) 223-233].
Corrigendum to "Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal" [Drug Discov. Today 22 (February (2)) (2017) 223-233]. Drug Discov Today. 2018 Jan 04;: Authors: Kuruva CS, Reddy PH PMID: 29306653 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - January 4, 2018 Category: Drugs & Pharmacology Authors: Kuruva CS, Reddy PH Tags: Drug Discov Today Source Type: research

Pathway-based technologies for early drug discovery.
Abstract Although the traditional drug discovery approach has led to the development of many successful drugs, the attrition rates remain high. Recent advances in systems-oriented approaches (systems-biology and/or pharmacology) and 'omics technologies has led to a plethora of new computational tools that promise to enable a more-informed and successful implementation of the reductionist, one drug for one target for one disease, approach. These tools, based on biomolecular pathways and interaction networks, offer a systematic approach to unravel the mechanism(s) of a disease and link them to the chemical space and...
Source: Drug Discovery Today - December 30, 2017 Category: Drugs & Pharmacology Authors: Fotis C, Antoranz A, Hatziavramidis D, Sakellaropoulos T, Alexopoulos LG Tags: Drug Discov Today Source Type: research

Real world big data for clinical research and drug development.
The objective of this paper is to identify the extent to which real world data (RWD) is being utilized, or could be utilized, at scale in drug development. Through screening peer-reviewed literature, we have cited specific examples where RWD can be used for biomarker discovery or validation, gaining a new understanding of a disease or disease associations, discovering new markers for patient stratification and targeted therapies, new markers for identifying persons with a disease, and pharmacovigilance. None of the papers meeting our criteria was specifically geared toward new novel targets or indications in the biopharmac...
Source: Drug Discovery Today - December 30, 2017 Category: Drugs & Pharmacology Authors: Singh G, Schulthess D, Hughes N, Vannieuwenhuyse B, Kalra D Tags: Drug Discov Today Source Type: research

One-Size-Fits-All Dosing in Oncology Wastes Money, Innovation and Lives.
Abstract Failure to individualize drug dosing may waste 50% of the value of pharmaceutical innovation coming off the bench, driving the unacceptable failure rates of drug development programs and unsustainable drug costs. An immense opportunity is thus presented to investors in pharmaceutical innovation who are willing to develop and field innovative Phase 1 trial methodologies that solve this problem. The principle of Dose Titration Algorithm Tuning (DTAT) offers a reasoned strategy for accomplishing this. PMID: 29170137 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 20, 2017 Category: Drugs & Pharmacology Authors: Norris DC Tags: Drug Discov Today Source Type: research

Recent advances in bacteriophage-based methods for bacteria detection.
Hołyst R Abstract Fast and reliable bacteria detection is crucial for lowering the socioeconomic burden related to bacterial infections (e.g., in healthcare, industry or security). Bacteriophages (i.e., viruses with bacterial hosts) pose advantages such as great specificity, robustness, toughness and cheap preparation, making them popular biorecognition elements in biosensors and other assays for bacteria detection. There are several possible designs of bacteriophage-based biosensors. Here, we focus on developments based on whole virions as recognition agents. We divide the review into sections dealing with phage...
Source: Drug Discovery Today - November 17, 2017 Category: Drugs & Pharmacology Authors: Richter Ł, Janczuk-Richter M, Niedziółka-Jönsson J, Paczesny J, Hołyst R Tags: Drug Discov Today Source Type: research

Understanding missing proteins: a functional perspective.
Abstract A missing protein (MP) is an unconfirmed genetic sequence for which a protein product is not yet detected. Currently, MPs are tiered based on supporting evidence mainly in the form of protein existence (PE) classification. As we discuss here, this definition is overly restrictive because proteins go missing in day-to-day proteomics as a result of low abundance, lack of sequence specificity, splice variants, and so on. Thus, we propose a broader functional classification of MPs that complements PE classification, discuss major causes, and examine three corresponding solution tiers:. biological, technical, ...
Source: Drug Discovery Today - November 17, 2017 Category: Drugs & Pharmacology Authors: Zhou L, Wong L, Goh WWB Tags: Drug Discov Today Source Type: research

Applications of stimuli-responsive nanoscale drug delivery systems in translational research.
Abstract Nanoscale drug delivery systems or nanocarriers have shown tremendous promise in the target-specific delivery of therapeutics as well as diagnostic agents. Additional properties can be introduced into nanocarriers to enhance the bioavailability and targeting efficiency of the transported drugs at diseased sites. Such nanocarriers are usually incorporated with stimuli-responsive components that can be triggered by specific stimuli (e.g., temperature, pH, or enzymes) and further induced by certain biological responses, such as enzyme hydrolysis and molecular conformational changes, leading to the controlled...
Source: Drug Discovery Today - November 16, 2017 Category: Drugs & Pharmacology Authors: Gu M, Wang X, Toh TB, Chow EK Tags: Drug Discov Today Source Type: research

The role of fMRI in drug development.
Abstract Functional magnetic resonance imaging (fMRI) has been known for over a decade to have the potential to greatly enhance the process of developing novel therapeutic drugs for prevalent health conditions. However, the use of fMRI in drug development continues to be relatively limited because of a variety of technical, biological, and strategic barriers that continue to limit progress. Here, we briefly review the roles that fMRI can have in the drug development process and the requirements it must meet to be useful in this setting. We then provide an update on our current understanding of the strengths and li...
Source: Drug Discovery Today - November 15, 2017 Category: Drugs & Pharmacology Authors: Carmichael O, Schwarz AJ, Chatham CH, Scott D, Turner JA, Upadhyay J, Coimbra A, Goodman JA, Baumgartner R, English BA, Apolzan JW, Shankapal P, Hawkins KR Tags: Drug Discov Today Source Type: research

Personalized nanomedicine for CNS diseases.
Abstract Central nervous system (CNS) diseases are rapidly increasing globally. Currently used therapeutic agents to treat CNS diseases exhibit significant efficacy. However, the inability of these drugs to cross the blood-brain barrier (BBB) and invasiveness of the technologies to achieve localized drug delivery in disease-specific parts of the brain have thwarted pain-free and complete treatment of CNS diseases. Therefore, the safe, non-invasive, and targeted delivery of drugs to the brain using nanoparticles (NPs) is currently receiving considerable research attention. Here, we highlight advances in state-of-th...
Source: Drug Discovery Today - November 15, 2017 Category: Drugs & Pharmacology Authors: Kaushik A, Jayant RD, Bhardwaj V, Nair M Tags: Drug Discov Today Source Type: research

Nanomedicine safety in preclinical and clinical development: focus on idiosyncratic injection/infusion reactions.
Abstract Injection/infusion reactions to nanopharmaceuticals (and particulate drug carriers) are idiosyncratic and well documented. The molecular basis of nanoparticle-mediated injection reactions is debatable, with two hypotheses as front-runners. The first is complement-activation-related 'pseudoallergy', where a causal role for nanoparticle-mediated complement activation in injection/infusion reactions is considered. However, the second hypothesis (the rapid phagocytic response hypothesis) states a transitional link from robust clearance of nanoparticles (NPs) from the blood by strategically placed responsive m...
Source: Drug Discovery Today - November 13, 2017 Category: Drugs & Pharmacology Authors: Moghimi SM Tags: Drug Discov Today Source Type: research

Fixed-dose combinations: a potential means to boost drug development for selected drugs.
PMID: 29146518 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 13, 2017 Category: Drugs & Pharmacology Authors: Oo C, Sy SKB Tags: Drug Discov Today Source Type: research

Drug Discovery Tomorrow: How to Catapult Ourselves into the Future.
PMID: 29146519 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 13, 2017 Category: Drugs & Pharmacology Authors: Molloy C Tags: Drug Discov Today Source Type: research

Galectin-3: mediator of microglia responses in injured brain.
riz J Abstract Galectin-3 is a pleiotropic protein involved in cell activation, proliferation and migration and plays a pivotal part as an inflammatory mediator in neurodegeneration. Galectin-3 is associated with microglial activation and proliferation after ischemia. Given its putative role as a dynamic fine-tuner of microglia, activation of Galectin-3 provides molecular cues in design of new immunomodulatory strategies for stroke management. This review summarizes recent evidence on the role of Galectin-3 as a mediator of immune responses in damaged brain and mechanisms employed by Galectin-3 to affect microglia...
Source: Drug Discovery Today - November 10, 2017 Category: Drugs & Pharmacology Authors: Rahimian R, Béland LC, Kriz J Tags: Drug Discov Today Source Type: research

Recent advances in galactose-engineered nanocarriers for the site-specific delivery of siRNA and anticancer drugs.
Abstract Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylat...
Source: Drug Discovery Today - November 9, 2017 Category: Drugs & Pharmacology Authors: Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, Shivhare US, Katare OP, Kesharwani P Tags: Drug Discov Today Source Type: research

Rare genetic diseases: update on diagnosis, treatment and online resources.
Abstract Rare genetic diseases collectively impact a significant portion of the world's population. For many diseases there is limited information available, and clinicians can find difficulty in differentiating between clinically similar conditions. This leads to problems in genetic counseling and patient treatment. The biomedical market is affected because pharmaceutical and biotechnology industries do not see advantages in addressing rare disease treatments, or because the cost of the treatments is too high. By contrast, technological advances including DNA sequencing and analysis, together with computer-aided ...
Source: Drug Discovery Today - November 9, 2017 Category: Drugs & Pharmacology Authors: Pogue RE, Cavalcanti DP, Shanker S, Andrade RV, Aguiar LR, Carvalho JL, Costa FF Tags: Drug Discov Today Source Type: research

Mesoporous silica nanoparticles: a smart nanosystem for management of breast cancer.
Abstract Breast cancer is the second-leading cause of death in women worldwide owing to aggressive metastasis, lack of early diagnosis and poor access to treatment amenities. During the past decade, mesoporous silica nanoparticles (MSNs) have gained ground for the delivery of a wide variety of chemotherapeutic and bioimaging agents owing to their unique characteristics and straightforward fabrication methods. Present research studies based on MSNs have provided various potential insights in their applicability in breast cancer treatment by improving solubility and stability and decreasing the adverse effects of cu...
Source: Drug Discovery Today - November 8, 2017 Category: Drugs & Pharmacology Authors: Poonia N, Lather V, Pandita D Tags: Drug Discov Today Source Type: research

What is precise pathophysiology in development of hypertension in pregnancy? Precision medicine requires precise physiology and pathophysiology.
Abstract It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. However, is the physiology of placental vessels the same as that of nonplacental vessels? What is the pathophysiology of placental vessels in development of pregnancy hypertension? This review aims to provide a comprehensive summary of special features of placental vascular regulations and the ...
Source: Drug Discovery Today - October 31, 2017 Category: Drugs & Pharmacology Authors: Gao Q, Tang J, Li N, Liu B, Zhang M, Sun M, Xu Z Tags: Drug Discov Today Source Type: research

Interfering peptides targeting protein-protein interactions: the next generation of drugs?
Abstract Protein-protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) - natural or synthetic peptides capable of interfering with PPIs - are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of an IP has been validated for several PPIs, generating great expectations for their t...
Source: Drug Discovery Today - October 30, 2017 Category: Drugs & Pharmacology Authors: Bruzzoni-Giovanelli H, Alezra V, Wolff N, Dong CZ, Tuffery P, Rebollo A Tags: Drug Discov Today Source Type: research

The ambivalent place of ethics in European regulatory documents.
PMID: 29081355 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - October 25, 2017 Category: Drugs & Pharmacology Authors: Bernabe RDLC, van Thiel GJMW, Gispen CC, Breekveldt NS, van Delden JJM Tags: Drug Discov Today Source Type: research

Fishing anti(lymph)angiogenic drugs with zebrafish.
te;-Beffa M Abstract Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angi...
Source: Drug Discovery Today - October 25, 2017 Category: Drugs & Pharmacology Authors: García-Caballero M, Quesada AR, Medina MA, Marí-Beffa M Tags: Drug Discov Today Source Type: research

Indacaterol/glycopyrronium: a dual bronchodilator for COPD.
Abstract Indacaterol/glycopyrronium (IND/GLY) 110/50mg was the first once-daily, long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). Development of IND/GLY was driven by the need to improve the standard of care for patients with this disease, in terms of symptom control and exacerbation frequency. IGNITE, an adaptive, comprehensive, and innovative Phase 3 development program, demonstrated the efficacy of IND/glycopyrronium in optimising bronchodilation, reducing symptoms, and r...
Source: Drug Discovery Today - October 24, 2017 Category: Drugs & Pharmacology Authors: Banerji D, Fogel R, Patalano F Tags: Drug Discov Today Source Type: research

3D nerve cell cultures and complex physiological relevance.
Abstract The field of tissue engineering has not yet provided knowledge on which a consensus for the complex physiological relevance (CPR) of neuronal cultures could be established. The CPR of 3D neuronal cultures can have a profound impact on the drug discovery process through the validation of in vitro models for the study of neuropsychiatric and degenerative diseases, as well as screening for neurotoxicity during drug development. Herein, we assemble evidence in support of the potential of [Ca(2+)]i oscillation frequency as a CPR outcome that can demonstrate the in vivo-like behavior of 3D cultures and differen...
Source: Drug Discovery Today - October 23, 2017 Category: Drugs & Pharmacology Authors: Cheng X, Ndyabawe K, Asthana A, Kisaalita WS Tags: Drug Discov Today Source Type: research

Gemcitabine and glioblastoma: challenges and current perspectives.
Abstract Gemcitabine is a nucleoside analog currently used for the treatment of various solid tumors as a single agent or in combination with other chemotherapeutic drugs. Its use against highly aggressive brain tumors (glioblastoma) has been evaluated in preclinical and clinical trials leading to controversial results. Gemcitabine can inhibit DNA chain elongation, is a potent radiosensitizer and it can enhance antitumor immune activity, but it also presents some drawbacks (e.g., short half-life, side effects, chemoresistance). The aim of this review is to discuss the challenges related to the use of gemcitabine f...
Source: Drug Discovery Today - October 23, 2017 Category: Drugs & Pharmacology Authors: Bastiancich C, Bastiat G, Lagarce F Tags: Drug Discov Today Source Type: research

Microarray patches: potentially useful delivery systems for long-acting nanosuspensions.
eta E Abstract Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for patients who are needle-phobic, given that injections have to be administered on a weekly or monthly basis. Needle-stick injuries, inappropriate reuse of needles, and poor disposal practices are major challenges in developing countries. Dissolving microneedles (MNs) are capable of deliver...
Source: Drug Discovery Today - October 23, 2017 Category: Drugs & Pharmacology Authors: Donnelly RF, Larrañeta E Tags: Drug Discov Today Source Type: research

Marketing authorisation of orphan medicines in Europe from 2000 to 2013.
Abstract An analysis was performed on a data set of 157 orphan designated medicines with an outcome for marketing authorisation application (MAA) between 2000 and 2013. The intention was to understand the factors associated with marketing authorisation success, the challenges developers face regarding orphan medicine development, and how scientific advice (SA) is used during development. The results demonstrated that orphan medicines have a lower success rate compared with non-orphan medicines and that determinants for marketing authorisation success were company size and compliance with SA. Compliance with SA cou...
Source: Drug Discovery Today - October 23, 2017 Category: Drugs & Pharmacology Authors: Hofer MP, Hedman H, Mavris M, Koenig F, Vetter T, Posch M, Vamvakas S, Regnstrom J, Aarum S Tags: Drug Discov Today Source Type: research

Computational drug repositioning for rare diseases in the era of precision medicine.
Abstract There are tremendous unmet needs in drug development for rare diseases. Computational drug repositioning is a promising approach and has been successfully applied to the development of treatments for diseases. However, how to utilize this knowledge and effectively conduct and implement computational drug repositioning approaches for rare disease therapies is still an open issue. Here, we focus on the means of utilizing accumulated genomic data for accelerating and facilitating drug repositioning for rare diseases. First, we summarize the current genome landscape of rare diseases. Second, we propose severa...
Source: Drug Discovery Today - October 18, 2017 Category: Drugs & Pharmacology Authors: Delavan B, Roberts R, Huang R, Bao W, Tong W, Liu Z Tags: Drug Discov Today Source Type: research

Insights from pharmacological similarity of epigenetic targets in epipolypharmacology.
Abstract As the number of compounds tested against epigenetic targets grows, exploration of the possible associations in chemical space among these targets could lead to the identification of new drugs or new designs of epipolypharmacological molecules. Thus, here we review the compound-epitarget associations of the numerous public databases available. Specifically, we explore the structure-multitarget activity relationships and diversity of over 7000 compounds tested against 52 epigenetic-related targets. We found that, whereas inhibitors of histone deacetylases and other epigenetic targets clustered in the chemi...
Source: Drug Discovery Today - October 13, 2017 Category: Drugs & Pharmacology Authors: Naveja JJ, Medina-Franco JL Tags: Drug Discov Today Source Type: research