Pharmaceutical cocrystals: from serendipity to design to application.
Abstract The field of pharmaceutical cocrystals has reached a tipping point, particularly because cocrystals can improve the physicochemical properties of drugs without compromising their therapeutic benefit. Accounts of cocrystal investigations in the literature started in earnest in 2003 and patent applications soon followed. The frequency of both has steadily accelerated, demonstrating an enhanced understanding of the design, characterisation, and manufacture of cocrystals and heightened interest from industry. Indeed, there were four new product approvals from 2014 to 2017 and more are in the pipeline. Here, w...
Source: Drug Discovery Today - December 3, 2018 Category: Drugs & Pharmacology Authors: Kavanagh ON, Croker DM, Walker GM, Zaworotko MJ Tags: Drug Discov Today Source Type: research

Behavior, experience, skill, and training: a four-pillar framework and tool for career development in science.
Abstract Technical expertise and a spirit of inquiry serve as cornerstones for a career in science. Within that career, there are multiple pathways across disciplines, therapeutic areas, and sectors. To optimize career planning, I showcase here a career development framework that integrates four pillars: behavior, experience, skill, and training (BEST). This framework encompasses interrelated elements that are crucial for career progression and reflects evolving priorities in today's network-oriented environment. Individuals can also leverage the framework as a tool to support short- and long-term career planning....
Source: Drug Discovery Today - December 3, 2018 Category: Drugs & Pharmacology Authors: Ashkenazy R Tags: Drug Discov Today Source Type: research

The drug repurposing landscape from 2012 to 2017: evolution, challenges, and possible solutions.
Abstract As the name suggests, drug repurposing is a strategy to identify new therapeutic uses for marketed drugs, discontinued and/or shelved drugs, and drug candidates currently in clinical development. Although not a recent concept, drug repurposing has gained momentum over the past few years and several drugs have been successfully repurposed. Here, we summarize the drug repurposing landscape from 2012 to 2017, with a major focus on repurposed drugs, collaborative opportunities, and funding opportunities specific to drug repurposing projects. Along with success stories, we also highlight the challenges and lim...
Source: Drug Discovery Today - December 1, 2018 Category: Drugs & Pharmacology Authors: Polamreddy P, Gattu N Tags: Drug Discov Today Source Type: research

Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?
Abstract The current main goal of diagnostic medicine is to detect crucial events in 'infinitely' small samples. The key question now is how to determine whether the rare cell events isolated and characterized from these samples reliably reflect the disease and heterogeneity of the tumor. In this review, we provide a short overview of the most recent methods developed for the isolation and characterization of rare cell events in clinical practice, with a specific focus on circulating tumor cells. We discuss the biological value to studying these cells at the single cell level and how these rare cell events can ref...
Source: Drug Discovery Today - November 26, 2018 Category: Drugs & Pharmacology Authors: Brown H, Tellez-Gabriel M, Cartron PF, Vallette F, Heymann MF, Heymann D Tags: Drug Discov Today Source Type: research

Phosphinic acids: current status and potential for drug discovery.
Abstract Phosphinic acid derivatives exhibit diverse biological activities and a high degree of structural diversity, rendering them a versatile tool in the development of new medicinal agents. Pronounced recent progress, coupled with previous research findings, highlights the impact of this moiety in medicinal chemistry. Here, we highlight the most important breakthroughs made with phosphinates with a range of pharmacological activities against many diseases, including anti-inflammatory, anti-Alzheimer, antiparasitic, antihepatitis, antiproliferative, anti-influenza, anti-HIV, antimalarial, and antimicrobial agen...
Source: Drug Discovery Today - November 24, 2018 Category: Drugs & Pharmacology Authors: Abdou MM, O'Neill PM, Amigues E, Matziari M Tags: Drug Discov Today Source Type: research

Meeting the discovery challenge of drug-resistant infections: progress and focusing resources.
Abstract Following multiple warnings from governments and health organisations, there has been renewed investment, led by the public sector, in the discovery of novel antimicrobials to meet the challenge of rising levels of drug-resistant infection, particularly in the case of resistance to antibiotics. Initiatives have also been announced to support and enable the antibiotic discovery process. In January 2018, the Medicines Discovery Catapult, UK, hosted a symposium: Next Generation Antibiotics Discovery, to consider the latest initiatives and any remaining challenges to inform and guide the international researc...
Source: Drug Discovery Today - November 23, 2018 Category: Drugs & Pharmacology Authors: Dougan G, Dowson C, Overington J, Next Generation Antibiotic Discovery Symposium Participants Tags: Drug Discov Today Source Type: research

Analysis of solvent-exposed and buried co-crystallized ligands: a case study to support the design of novel protein-protein interaction inhibitors.
Abstract Molecular descriptors have been used to characterize and predict the functions of small molecules, including inhibitors of protein-protein interactions (iPPIs). Such molecules are valuable to investigate disease pathways and as starting points for drug discovery endeavors. iPPIs tend to bind at the surface of macromolecules and the design of such compounds remains challenging. Here, we report on our investigation of a pool of interpretable molecular descriptors for solvent-exposed and buried co-crystallized ligands. Several descriptors were found to be significantly different between the two classes and w...
Source: Drug Discovery Today - November 22, 2018 Category: Drugs & Pharmacology Authors: Trisciuzzi D, Nicolotti O, Miteva MA, Villoutreix BO Tags: Drug Discov Today Source Type: research

Artificial intelligence in drug development: present status and future prospects.
Abstract Artificial intelligence (AI) uses personified knowledge and learns from the solutions it produces to address not only specific but also complex problems. Remarkable improvements in computational power coupled with advancements in AI technology could be utilised to revolutionise the drug development process. At present, the pharmaceutical industry is facing challenges in sustaining their drug development programmes because of increased R&D costs and reduced efficiency. In this review, we discuss the major causes of attrition rates in new drug approvals, the possible ways that AI can improve the efficie...
Source: Drug Discovery Today - November 22, 2018 Category: Drugs & Pharmacology Authors: Mak KK, Pichika MR Tags: Drug Discov Today Source Type: research

Advancing nonclinical innovation and safety in pharmaceutical testing.
Abstract Nonclinical tests are considered crucial for understanding the safety of investigational medicines. However, the effective translation from nonclinical to human application is limited and must be improved. Drug development stakeholders are working to advance human-based in vitro and in silico methods that might be more predictive of human efficacy and safety in vivo because they enable scientists to model the direct interaction of drugs with human cells, tissues, and biological processes. Here, we recommend test-neutral regulations; increased funding for development and integration of human-based approach...
Source: Drug Discovery Today - November 20, 2018 Category: Drugs & Pharmacology Authors: Baker EJ, Beck NA, Berg EL, Clayton-Jeter HD, Chandrasekera PC, Curley JL, Donzanti BA, Ewart LC, Gunther JM, Kenna JG, LeCluyse EL, Liebman MN, Pugh CL, Watkins PB, Sullivan KM Tags: Drug Discov Today Source Type: research

A review of non-invasive insulin delivery systems for diabetes therapy in clinical trials over the past decade.
Abstract At present, the main form of insulin administration is the invasive subcutaneous (s.c.) route and, for many patients, this means managing their glucose levels with multiple daily injections, which is both painful and difficult to administer chronically. To increase patient compliance, products are slowly reaching the market that are more patient friendly, such as the insulin patch-pump systems, including Omnipod and V-Go, but also the inhaled-insulin Afrezza® and the buccal insulin Oral-lyn™. In this review, we outline the history of insulin, the various options that are currently available in p...
Source: Drug Discovery Today - November 19, 2018 Category: Drugs & Pharmacology Authors: Easa N, Alany R, Carew M, Vangala A Tags: Drug Discov Today Source Type: research

Pharmacophore-based models for therapeutic drugs against phosphorylated tau in Alzheimer's disease.
This article also addresses 3D pharmacophore-based drug models designed to treat patients with AD and other tauopathies. PMID: 30453058 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 16, 2018 Category: Drugs & Pharmacology Authors: Pradeepkiran JA, Reddy AP, Reddy PH Tags: Drug Discov Today Source Type: research

Gut reaction: impact of systemic diseases on gastrointestinal physiology and drug absorption.
Abstract It was in 400 BC that Hippocrates reportedly stated that "death sits in the colon". The growth in our knowledge of the intestinal microbiome and the gut-brain axis, their function and imbalance, has distinctly uncovered the complex relationship between the gut to disease predisposition and development, heralding the problem and the solution to disease pathology. Human studies of new drug molecules are typically performed in healthy volunteers and their specific disease indication. Approved drugs, however, are used by patients with diverse disease backgrounds. Here, we review the current literatu...
Source: Drug Discovery Today - November 16, 2018 Category: Drugs & Pharmacology Authors: Hatton GB, Madla CM, Rabbie SC, Basit AW Tags: Drug Discov Today Source Type: research

Impact of dosing schedule in animal models on compound progression decisions.
PMID: 30448352 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 15, 2018 Category: Drugs & Pharmacology Authors: Chen C Tags: Drug Discov Today Source Type: research

Accelerating pharmaceutical structure-guided drug design: a successful model.
Abstract The impact and value of structure-based drug design to pharmaceutical discovery across the industry are now undeniable, with many break-through therapies on the market that are structure based in nature. Enabling the structural research is the Industrial Macromolecular Crystallography Association-Collaborative Access Team (IMCA-CAT), formed over 25 years ago as a world-class research facility at the synchrotron at Argonne National Laboratory. What makes IMCA-CAT unique is the strategy of the founding consortium to comprehensively provide for the evolving needs of industry in one facility. This includes ye...
Source: Drug Discovery Today - November 15, 2018 Category: Drugs & Pharmacology Authors: Keefe LJ, Stoll VS Tags: Drug Discov Today Source Type: research

A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.
Abstract Mood disorders represent the largest cause of disability worldwide. The monoaminergic deficiency hypothesis, which has dominated the conceptual framework for researching the pathophysiology of mood disorders and the development of novel treatment strategies, cannot fully explain the underlying neurobiology of mood disorders. Mounting evidence collected over the past two decades suggests the amino acid neurotransmitter systems (glutamate and GABA) serve central roles in the pathophysiology of mood disorders. Here, we review progress in the development of compounds that act on these systems as well as their...
Source: Drug Discovery Today - November 14, 2018 Category: Drugs & Pharmacology Authors: Wilkinson ST, Sanacora G Tags: Drug Discov Today Source Type: research

Role of MIF and D-DT in immune-inflammatory, autoimmune, and chronic respiratory diseases: from pathogenic factors to therapeutic targets.
i F Abstract Macrophage migration inhibitory factor (MIF) is a protein that acts as a cytokine-, enzyme-, endocrine- and chaperon-like molecule. It binds to the cell-surface receptor CD74 in association with CD44, which activates the downstream signal transduction pathway. In addition, MIF acts also as a noncognate ligand for C-X-C chemokine receptor type 2(CXCR2), CXCR4, and CXCR7. Recently, D-dopachrome tautomerase (D-DT), a second member of the MIF superfamily, was identified. From a pharmacological and clinical point of view, the nonredundant biological properties of MIF and D-DT anticipate potential synergism...
Source: Drug Discovery Today - November 12, 2018 Category: Drugs & Pharmacology Authors: Günther S, Fagone P, Jalce G, Atanasov A, Guignabert C, Nicoletti F Tags: Drug Discov Today Source Type: research

Toward improving drug delivery research in Egypt: Cancer Nanotechnology Research Laboratory as a role model.
PMID: 30439448 [PubMed - as supplied by publisher] (Source: Drug Discovery Today)
Source: Drug Discovery Today - November 12, 2018 Category: Drugs & Pharmacology Authors: Elzoghby AO, Freag MS Tags: Drug Discov Today Source Type: research

The essentiality of drug targets: an analysis of current literature and genomic databases.
Abstract Essential genes encode proteins thought to be crucial for the survival of an organism. However, the role of essential genes in human disease and their suitability as drug targets is less clear. Here, we use a recent catalog of nearly 9000 known essential and nonessential genes to evaluate their involvement as therapeutic targets in human diseases. We find that essential genes are more likely than nonessential genes to play a part in specific therapeutic areas such as cardiovascular diseases and neoplasms. We also find significant differences between essential and nonessential genes among protein classes r...
Source: Drug Discovery Today - November 12, 2018 Category: Drugs & Pharmacology Authors: Ji X, Rajpal DK, Freudenberg JM Tags: Drug Discov Today Source Type: research

Strategies for brain-targeting liposomal delivery of small hydrophobic molecules in the treatment of neurodegenerative diseases.
Abstract Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecules have been shown to be promising in preclinical studies. However, the major challenge for brain-targeting drugs is how to efficiently deliver the drugs across the blood-brain barrier (BBB) to desired targets. To address this issue, liposomal delivery systems have proved to be ideal carriers...
Source: Drug Discovery Today - November 8, 2018 Category: Drugs & Pharmacology Authors: Wang ZY, Sreenivasmurthy SG, Song JX, Liu J, Li M Tags: Drug Discov Today Source Type: research

Growing synergy of nanodiamonds in neurodegenerative interventions.
Abstract Neurodegenerative diseases are complex in both their nature and prognosis. The difficulties associated with penetrating the blood-brain barrier (BBB), achieving site-specific targeting to the brain, and identifying the genetic etiologies responsible make treating neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and stroke, challenging. The aim to treat disease at the molecular level has galvanized nanotechnology research. Among the forms of nanoparticles (NPs) explored thus far, nanodiamonds (NDs) have s...
Source: Drug Discovery Today - November 5, 2018 Category: Drugs & Pharmacology Authors: Saraf J, Kalia K, Bhattacharya P, Tekade RK Tags: Drug Discov Today Source Type: research

Interplay between hereditary and environmental factors to establish an in vitro disease model of keratoconus.
Abstract Keratoconus (KC) is a bilateral corneal dystrophy and a multifactorial, multigenic disorder with an etiology involving a strong environmental component and complex inheritance patterns. The underlying pathophysiology of KC is poorly understood because of potential crosstalk between genetic-epigenetic variants possibly triggered by the environmental factors. Here, we decode the etiopathological basis of KC using genomic, transcriptomic, proteomic and metabolic approaches. The lack of relevant models that accurately imitate this condition has been particularly limiting in terms of the effective management o...
Source: Drug Discovery Today - November 5, 2018 Category: Drugs & Pharmacology Authors: Roy S, Yadav S, Dasgupta T, Chawla S, Tandon R, Ghosh S Tags: Drug Discov Today Source Type: research

Therapeutic potential of endogenous stem cells and cellular factors for scar-free skin regeneration.
Abstract Injured human skin fails to regenerate, resulting in scar formation. Annually, 100 million new skin-scarring incidents, occurring as a result of surgery, disease, burns, or sports-related damage, remain untreated. Here, we review knowledge gained from scar-free experimental animal models that have natural regenerative mechanisms for scar-free skin recovery. We also focus on the unique role of endogenous stem cells and other cellular and molecular factors, including the balance of the transforming growth factor-beta (TGF-β) pathway in the context of human skin regeneration. This new strategy opens a n...
Source: Drug Discovery Today - November 5, 2018 Category: Drugs & Pharmacology Authors: Giri S, Machens HG, Bader A Tags: Drug Discov Today Source Type: research

Evolution of commercially available compounds for HTS.
Abstract Over recent years, an industry of compound suppliers has grown to provide drug discovery with screening compounds: it is estimated that there are over 16 million compounds available from these sources. Here, we review the chemical space covered by suppliers' compound libraries (SCL) in terms of compound chemophysical properties, novelty, diversity, and quality. We examine the feasibility of compiling high-quality vendor-based libraries avoiding complicated, expensive compound management activity, and compare the resulting libraries to the ChEMBL data set. We also consider how vendors have responded to the...
Source: Drug Discovery Today - November 3, 2018 Category: Drugs & Pharmacology Authors: Volochnyuk DM, Ryabukhin SV, Moroz Y, Savych O, Chuprina A, Horvath D, Zabolotna Y, Varnek A, Judd DB Tags: Drug Discov Today Source Type: research

Microtransplantation of human brain receptors into oocytes to tackle key questions in drug discovery.
Abstract It is important in drug discovery to demonstrate that activity of novel drugs found by screening on recombinant receptors translates to activity on native human receptors in brain areas affected by disease. In this review, we summarise the development and use of the microtransplantation technique. Native receptors are reconstituted from human brain tissues into oocytes from the frog Xenopus laevis where they can be functionally assessed. Oocytes microtransplanted with hippocampal tissue from an epileptic patient were used to demonstrate that new antiepileptic agents act on receptors in diseased tissue. Fu...
Source: Drug Discovery Today - November 3, 2018 Category: Drugs & Pharmacology Authors: Zwart R, Mazzo F, Sher E Tags: Drug Discov Today Source Type: research

Micro- and nano-formulations for bioprinting and additive manufacturing.
Crauste-Manciet S Abstract Recent developments in bioprinting have enabled an optimized formulation of bioinks by incorporating pharmaceuticals into cell-containing gel matrices. The proof-of-printability of a variety of forms has been provided, such as particles and fibers in the nanometric or micrometric range like dendrimers or micelles, although this is still lacking for some (liposomes for example). Resulting composite bioinks have the advantage of (i) improving cell growth and differentiation, (ii) delivering active molecules or (iii) improving mechanical properties of bioinks, printed scaffolds or the print...
Source: Drug Discovery Today - October 31, 2018 Category: Drugs & Pharmacology Authors: Bouguéon G, Kauss T, Dessane B, Barthélémy P, Crauste-Manciet S Tags: Drug Discov Today Source Type: research

FoxO1-miRNA interacting networks as potential targets for mitochondrial diseases.
Abstract Mitochondrial homeostasis is important for the health and well-being of organ systems and organisms. Mitochondrial dysfunction is known to be the cause and consequence of metabolic diseases, including obesity, diabetes, cancer, neurodegeneration, cerebrovascular, and cardiovascular disease. For cardiovascular tissue, which relies mostly on oxidative phosphorylation, the role of mitochondria is inevitable. Rather than being biomarkers of mitochondrial health, miRNAs are now known as bioregulators of this important feature. Recent studies have shown a close interaction between Forkhead box other 1 (FoxO1) t...
Source: Drug Discovery Today - October 24, 2018 Category: Drugs & Pharmacology Authors: Puthanveetil P Tags: Drug Discov Today Source Type: research

Using molecular-mimicry-inducing pathways of pathogens as novel drug targets.
Abstract Several microbial pathogens cause autoimmune diseases in humans by exhibiting molecular mimicry with the host proteins. However, the contribution of autoimmunity in microbial pathogenesis has not been evaluated critically. Clinical and experimental observations have supported and corroborated that autoimmunity was a fundamental process underlying pathology of human tuberculosis bacteria. In the current review, we propose novel drug targets based on a pathogen's molecular-mimicry-inducing proteins. The process for identification of drug targets has been explained using Mycobacterium tuberculosis as a model...
Source: Drug Discovery Today - October 23, 2018 Category: Drugs & Pharmacology Authors: Garg A, Kumari B, Singhal N, Kumar M Tags: Drug Discov Today Source Type: research

The power of combining phenotypic and target-focused drug discovery.
Abstract A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of available in vitro TD methods, the task of matching a phenotypically active compound with a biomolecular target remains challenging. Consequently, this review details the latest developments of in silico techniques that expedite TD. Ultimately, the deconvoluted target allows us to reap the be...
Source: Drug Discovery Today - October 22, 2018 Category: Drugs & Pharmacology Authors: Heilker R, Lessel U, Bischoff D Tags: Drug Discov Today Source Type: research

Advances in particle shape engineering for improved drug delivery.
Abstract Spherical particles such as liposomes and microspheres are the most common and extensively applied drug vehicles. However, researchers have come to realize the superiority of nonspherical nanoparticles. Actually, in human bodies red blood cells, gut biotics and many well-known pathogens have distinct shapes. It can be reasonably inferred that particle shape plays a pivotal part in human bodies. In this review, we summarize the recent studies about the effect of shape on delivery processes such as cellular uptake, tissue penetration and biodistribution. The underlying mechanisms that are relevant to the ph...
Source: Drug Discovery Today - October 17, 2018 Category: Drugs & Pharmacology Authors: Yang Y, Nie D, Liu Y, Yu M, Gan Y Tags: Drug Discov Today Source Type: research

Accomplishments and challenges in stem cell imaging in vivo.
Abstract Stem cell therapies have demonstrated promising preclinical results, but very few applications have reached the clinic owing to safety and efficacy concerns. Translation would benefit greatly if stem cell survival, distribution and function could be assessed in vivo post-transplantation, particularly in patients. Advances in molecular imaging have led to extraordinary progress, with several strategies being deployed to understand the fate of stem cells in vivo, for example using magnetic resonance, scintigraphy, PET, ultrasound and optical imaging. Here, we review the recent advances, challenges and futur...
Source: Drug Discovery Today - October 17, 2018 Category: Drugs & Pharmacology Authors: Bose RJC, Mattrey RF Tags: Drug Discov Today Source Type: research

Artificial intelligence and its potential in oncology.
Abstract The two main branches associated with Artificial Intelligence (AI) in medicine are virtual and physical. The virtual component includes machine learning (ML) and algorithms, whereas physical AI includes medical devices and robots for delivering care. AI is used successfully in tumour segmentation, histopathological diagnosis, tracking tumour development, and prognosis prediction. CURATE.AI, developed at the National University of Singapore, is a platform that automatically decides the optimum dose of drugs for a durable response, allowing the patient to resume a completely normal life. With the involvemen...
Source: Drug Discovery Today - October 17, 2018 Category: Drugs & Pharmacology Authors: Londhe VY, Bhasin B Tags: Drug Discov Today Source Type: research

Can lifecycle management safeguard innovation in the pharmaceutical industry?
Abstract The pharmaceutical industry invests enormous amounts of resources (>€1 billion and>10years) in the development of new products. External factors such as intensifying foreign competition and greater regulatory demands can negatively affect the profit margin, whereas the R&D productivity diminishes. To stay competitive and to maintain high R&D capabilities for developing new medicinal products, companies must make smart investment decisions to maximize their return on investment. Consequently, the entire lifecycle of a medicinal product must be effectively managed to ensure a sustained de...
Source: Drug Discovery Today - October 17, 2018 Category: Drugs & Pharmacology Authors: Hering S, Loretz B, Friedli T, Lehr CM, Stieneker F Tags: Drug Discov Today Source Type: research

Targeting VEGF-neuropilin interactions: a promising antitumor strategy.
Abstract Inhibition of vascular endothelial growth factor (VEGF) or its corresponding receptor (VEGFR) has been validated as an efficacious antiangiogenetic approach for cancer treatment. More recently, neuropilins (NRPs), the essential coreceptors for VEGF, have also been shown to have a significant role in VEGF signaling. Given the multifaceted effects of VEGF-NRP interactions on tumor initiation and progression, the exploration of new chemical entities that selectively block these interactions has recently attracted considerable interest as a novel antitumor strategy. Here, we summarize the biological functions...
Source: Drug Discovery Today - October 11, 2018 Category: Drugs & Pharmacology Authors: Peng K, Bai Y, Zhu Q, Hu B, Xu Y Tags: Drug Discov Today Source Type: research

Towards the development of human immune-system-on-a-chip platforms.
Abstract Organ-on-a-chip (OoCs) platforms could revolutionize drug discovery and might ultimately become essential tools for precision therapy. Although many single-organ and interconnected systems have been described, the immune system has been comparatively neglected, despite its pervasive role in the body and the trend toward newer therapeutic products (i.e., complex biologics, nanoparticles, immune checkpoint inhibitors, and engineered T cells) that often cause, or are based on, immune reactions. In this review, we recapitulate some distinctive features of the immune system before reviewing microfluidic device...
Source: Drug Discovery Today - October 9, 2018 Category: Drugs & Pharmacology Authors: Polini A, Mercato LLD, Barra A, Zhang YS, Calabi F, Gigli G Tags: Drug Discov Today Source Type: research

Application of nanotechnology to improve the therapeutic benefits of statins.
Abstract Hyperlipidemia is defined as an elevated level of lipids and lipoproteins in the blood and is considered to be a significant risk factor for accelerating the process of atherosclerosis and, consequently, cardiovascular disease. The level of cholesterol, especially low-density lipoprotein cholesterol (LDL-C), is commonly elevated in hyperlipidemia and represents the primary therapeutic target. Statins are a group of drugs that function by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and are extremely efficacious in reducing elevated LDL-C in the serum and preventing atherosclerotic ...
Source: Drug Discovery Today - October 5, 2018 Category: Drugs & Pharmacology Authors: Korani S, Korani M, Bahrami S, Johnston TP, Butler AE, Banach M, Sahebkar A Tags: Drug Discov Today Source Type: research

Peptide-based therapeutics: quality specifications, regulatory considerations, and prospects.
Abstract Exquisite selectivity, remarkable efficacy, and minimal toxicity are key attributes inherently assigned to peptides, resulting in increased research interest from the pharmaceutical industry in these peptide-based therapeutics (PbT). Pharmacopoeias are used to develop authoritative standards for PbT by providing standard specifications and test methods. Nevertheless, a lack of harmonization in test procedures adopted for PbT in the latest editions of Pharmacopoeias has been observed. Adoption of a harmonized monograph could increase further the interest of the global pharmaceutical industry in PbTs. Here,...
Source: Drug Discovery Today - October 5, 2018 Category: Drugs & Pharmacology Authors: Rastogi S, Shukla S, Kalaivani M, Singh GN Tags: Drug Discov Today Source Type: research

Implications of human induced pluripotent stem cells in metabolic disorders: from drug discovery toward precision medicine.
Diaz-Martinez NE Abstract Human induced pluripotent stem cells (hiPSCs) enable in vitro high-throughput pharmacological screening assays of diseased tissue. Together with recent genome-wide association studies (GWAS), hiPSCs enable the identification of key mutations for the development of effective treatments based on precise drugs. In concert with CRISPR/Cas9 systems, hiPSC technology can reveal therapeutic targets in metabolic disorders. The ex vivo CRISPR correction of autologous patient-derived hiPSCs has led to the development of replacement cell therapies, providing better patient prognoses. PMID: 302...
Source: Drug Discovery Today - October 4, 2018 Category: Drugs & Pharmacology Authors: Cota-Coronado A, Ramírez-Rodríguez PB, Padilla-Camberos E, Diaz NF, Flores-Fernández JM, Avila-Gonzalez D, Diaz-Martinez NE Tags: Drug Discov Today Source Type: research

Design strategies for chemical-stimuli-responsive programmable nanotherapeutics.
Abstract Chemical-stimuli-responsive nanotherapeutics have gained great interest in drug delivery and diagnosis applications. These nanotherapeutics are designed to respond to specific internal stimuli including pH, ionic strength, redox, reactive oxygen species, glucose, enzymes, ATP and hypoxia for site-specific and responsive or triggered release of payloads and/or biomarker detections. This review systematically and comprehensively addresses up-to-date technological and design strategies, and challenges nanomaterials to be used for triggered release and sensing in response to chemical stimuli. PMID: 30292...
Source: Drug Discovery Today - October 4, 2018 Category: Drugs & Pharmacology Authors: Gulfam M, Sahle FF, Lowe TL Tags: Drug Discov Today Source Type: research

Antithrombotic P2Y12 receptor antagonists: recent developments in drug discovery.
CE Abstract The P2Y12 receptor is one of eight known P2Y receptor subtypes, and belongs to the G-protein-coupled receptor (GPCR) family. The P2Y12 receptor is highly expressed on blood platelets and in the brain. Potent, selective, peripherally acting antagonists for the P2Y12 receptor are used clinically as antithrombotic drugs. Several different scaffolds have been identified as P2Y12 receptor antagonists, including irreversibly acting thienotetrahydropyridines (prodrugs), and reversible competitive antagonists, including adenine nucleotide analogs, piperazinyl-glutamate-quinolines, -pyridines, and -pyrimidines...
Source: Drug Discovery Today - October 3, 2018 Category: Drugs & Pharmacology Authors: Baqi Y, Müller CE Tags: Drug Discov Today Source Type: research

The future R & D landscape in non-alcoholic steatohepatitis (NASH).
The future R&D landscape in non-alcoholic steatohepatitis (NASH). Drug Discov Today. 2018 Oct 03;: Authors: Black D, Brockbank S, Cruwys S, Goldenstein K, Hein P, Humphries B Abstract Nonalcoholic steatohepatitis (NASH) is emerging as a major public health issue for the 21st century and is associated with significant liver-related morbidity and mortality. At present, there are no approved drug therapies for NASH. Consequently, NASH has become the focus of significant public and private research and development. In this review, we highlight the research and development (R&D) challenges and oppo...
Source: Drug Discovery Today - October 3, 2018 Category: Drugs & Pharmacology Authors: Black D, Brockbank S, Cruwys S, Goldenstein K, Hein P, Humphries B Tags: Drug Discov Today Source Type: research

Targeting intrinsically disordered proteins at the edge of chaos.
Abstract Intrinsically disordered proteins or intrinsically disordered regions (IDPs or IDRs) are those that do not fold into defined tertiary structures under physiological conditions. Given their prevalence in various diseases, IDPs are attractive therapeutic targets. However, because of the dynamic nature of the IDP structure, conventional structure-based drug design methods cannot be directly applied. Thanks to recent progress in understanding the mechanisms underlying IDP and ligand interactions, computational strategies for IDP-targeted rational drug discovery are emerging. Here, we summarize recent developm...
Source: Drug Discovery Today - September 29, 2018 Category: Drugs & Pharmacology Authors: Ruan H, Sun Q, Zhang W, Liu Y, Lai L Tags: Drug Discov Today Source Type: research

Basic and practical concepts of radiopharmaceutical purification methods.
Abstract The presence of radiochemical impurities in a radiopharmaceutical contributes to an unnecessary radiation burden for the patients or to an undesirable high radioactivity background, which reduces the imaging contrast or therapeutic efficacy. Therefore, if the radiolabeling process results in unsatisfactory radiochemical purity, a purification step is unavoidable. A successful purification process requires a profound knowledge about the radiopharmaceuticals of interest ranging from structural features to susceptibility to different conditions. Most radiopharmaceutical purification methods are based on chro...
Source: Drug Discovery Today - September 29, 2018 Category: Drugs & Pharmacology Authors: Molavipordanjani S, Tolmachev V, Hosseinimehr SJ Tags: Drug Discov Today Source Type: research

Factors and situations influencing the value of patient preference studies along the medical product lifecycle: a literature review.
s I Abstract Industry, regulators, health technology assessment (HTA) bodies, and payers are exploring the use of patient preferences in their decision-making processes. In general, experience in conducting and assessing patient preference studies is limited. Here, we performed a systematic literature search and review to identify factors and situations influencing the value of patient preference studies, as well as applications throughout the medical product lifecyle. Factors and situations identified in 113 publications related to the organization, design, and conduct of studies, and to communication and use of ...
Source: Drug Discovery Today - September 26, 2018 Category: Drugs & Pharmacology Authors: van Overbeeke E, Whichello C, Janssens R, Veldwijk J, Cleemput I, Simoens S, Juhaeri J, Levitan B, Kübler J, de Bekker-Grob E, Huys I Tags: Drug Discov Today Source Type: research

Considerations for implementing an informatics system to support biologics drug discovery.
Abstract A comprehensive, well-functioning and scientifically aware informatics environment is of the utmost importance in supporting effective drug discovery programs. However, implementing such a system can, without a carefully crafted and enacted strategy, be a disruptive and time-consuming process, fraught with risks of cost overruns and the potential to end up with a system that ultimately does not meet the ever-evolving needs of the organization. In this review, using our experience from the software provider perspective, we discuss how a drug discovery organization should approach the task of selecting an i...
Source: Drug Discovery Today - September 26, 2018 Category: Drugs & Pharmacology Authors: LeBeau AP Tags: Drug Discov Today Source Type: research

Fungal immunomodulatory proteins: characteristic, potential antitumor activities and their molecular mechanisms.
Abstract During recent decades,>30 fungal immunomodulatory proteins (FIPs) have been found in a range of mushrooms and other fungi. Various pharmacological functions of FIPs have become important in the discovery and development of new drugs. In this review, we discuss some important factors, focusing on the use of amino acid sequence data to predict structural and physicochemical properties. We also discuss pharmacologic activities and possible mechanisms of the proteins with a focus on antitumor activities. Numerous other questions must also be addressed before FIPs can be widely accepted and used as antitumo...
Source: Drug Discovery Today - September 25, 2018 Category: Drugs & Pharmacology Authors: Li QZ, Zheng YZ, Zhou XW Tags: Drug Discov Today Source Type: research

Small molecules for fat combustion: targeting thermosensory and satiety signals in the central nervous system.
Abstract Brown adipose tissue (BAT) dissipates fatty acids as heat to maintain body temperature in cold environments. The existence of BAT and beige cells in human adults supplies a promising weight-reduction therapy. The central thermogenic regulation descends through an excitatory neural pathway from the hypothalamus, medullar and spine toward BAT. This sympathoexcitatory thermogenic circuit is controlled by GABAergic (γ-aminobutyric acid) signaling from the thermoregulatory center in the preoptic area and the satiety center in the ventromedial nucleus of the hypothalamus. This review summarizes recent res...
Source: Drug Discovery Today - September 21, 2018 Category: Drugs & Pharmacology Authors: Liu J, Lin L Tags: Drug Discov Today Source Type: research

Bile acid homeostasis paradigm and its connotation with cholestatic liver diseases.
Abstract Bile acid (BA) has an important role in signal transduction, and has clinical applicability as an early biomarker for the diagnosis and prevention of cholestatic liver disease, which has a close relationship with BA homeostasis. Understanding the guarantee factors, function, and regulation of BA homeostasis under physiological conditions and in cholestatic liver diseases could provide novel therapeutic approaches for treating cholestatic liver injury. Here, we review potential biomarkers of BA, and new therapeutic approaches and the latest therapeutic drugs for cholestasis. We believe that the molecular m...
Source: Drug Discovery Today - September 19, 2018 Category: Drugs & Pharmacology Authors: Yang T, Khan GJ, Wu Z, Wang X, Zhang L, Jiang Z Tags: Drug Discov Today Source Type: research

Functionalizing bioinks for 3D bioprinting applications.
Abstract 3D bioprinting has emerged as the intersection between chemistry, biology and technology. Through its integration of cells, biocompatible materials and robotic-controlled dispensing systems, the process enables the production of structures that are biomimetic and functional, thus revolutionizing the concept of tissue engineering. One of the biggest limitations of 3D bioprinting for tissue engineering is the lack of printable materials (bioinks) with all-inclusive properties desirable for the construction of engineered 'bio-physico-functional' tissues and organs. Thus, bioinks are required to be functional...
Source: Drug Discovery Today - September 19, 2018 Category: Drugs & Pharmacology Authors: Parak A, Pradeep P, du Toit LC, Kumar P, Choonara YE, Pillay V Tags: Drug Discov Today Source Type: research

Safety differentiation: emerging competitive edge in drug development.
Abstract With increasing expectations to provide evidence of drug efficacy, safety, and cost-effectiveness, best-in-class drugs are a major value driver for the pharmaceutical industry. Superior safety is a key differentiation criterion that could be achieved through better risk:benefit profiles, safety margins, fewer contraindications, and improved patient compliance. To accomplish this, comparative safety assessments using innovative and adaptive nonclinical and clinical outcome-based approaches should be undertaken, and continuous strategic adjustments must be made as the risk:benefit profiles evolve. Key succe...
Source: Drug Discovery Today - September 19, 2018 Category: Drugs & Pharmacology Authors: Uteng M, Urban L, Brees D, Muller PY, Kullak-Ublick GA, Bouchard P, Tougas G, Chibout SD Tags: Drug Discov Today Source Type: research

Biosimilar medicines used for cancer therapy in Europe: a review.
This article provides an updated review of the biosimilar medicines approved for cancer therapy in the European Union (EU). First we discuss the most relevant aspects for the development and approval of biosimilar medicines. We then present the oncological biosimilar drugs currently used, which include epoetins (alpha and zeta), filgrastim, and monoclonal antibodies (rituximab, trastuzumab and bevacizumab). Among the clinical applications of biosimilar medicines, cancer therapy remains the main target area and more approved biosimilars are expected over the next few years, providing cost-effective drugs to more patients. F...
Source: Drug Discovery Today - September 19, 2018 Category: Drugs & Pharmacology Authors: Santos SB, Sousa Lobo JM, Silva AC Tags: Drug Discov Today Source Type: research