abstract：:14-3-3 proteins regulate intracellular signaling pathways, such as signal transduction, protein trafficking, cell cycle, and apoptosis. In addition to the ubiquitous roles of 14-3-3 isoforms, unique tissue-specific functions are also described for each isoform. Owing to their role in regulating cell cycle, protein tra...

journal_title：Drug discovery today

authors： Aghazadeh Y,Papadopoulos V

更新日期：2016-02-01 00:00:00

abstract：:Following the introduction of antibiotic therapy and widespread inoculations, cardiovascular diseases have leapt ahead of infectious diseases in terms of prevalence in much of the developed and developing world. Herein, we assess FDA-approved drugs for the treatment of cardiovascular diseases. The drug development ent...

journal_title：Drug discovery today

authors： Kinch MS,Surovtseva Y,Hoyer D

更新日期：2016-01-01 00:00:00

abstract：:New precompetitive ways of working in the pharmaceutical industry are driving the development of new informatics systems to enable their execution and management. The European Lead Factory (ELF) is a precompetitive, 30-partner collaboration between academic groups, small-medium enterprises and pharmaceutical companies...

journal_title：Drug discovery today

authors： Paillard G,Cochrane P,Jones PS,van Hoorn WP,Caracoti A,van Vlijmen H,Pannifer AD

更新日期：2016-01-01 00:00:00

abstract：:A rapid expansion in precision medicine founded on the potential for durable clinical benefit through matching a drug to a predictive marker used to select patients has driven the development of targeted drugs with accompanied companion diagnostics for patient selection. Oncology has been at the forefront, with the im...

journal_title：Drug discovery today

authors： Hollingsworth SJ

更新日期：2015-12-01 00:00:00

abstract：:The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified...

journal_title：Drug discovery today

authors： Trusheim MR,Berndt ER

更新日期：2015-12-01 00:00:00

abstract：:Of the three viral enzymes essential to HIV replication, HIV-1 integrase (IN) is gaining popularity as a target for the antiviral therapy of AIDS. Substantial work focusing on IN has been done over the past three decades, which has facilitated and led to the approval of three drugs. Here, we discuss in detail the deve...

journal_title：Drug discovery today

authors： Su M,Tan J,Lin CY

更新日期：2015-11-01 00:00:00

abstract：:We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...

journal_title：Drug discovery today

authors： Polanski J,Bogocz J,Tkocz A

更新日期：2015-11-01 00:00:00

abstract：:Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exception...

journal_title：Drug discovery today

authors： Folkersen L,Biswas S,Frederiksen KS,Keller P,Fox B,Fleckner J

更新日期：2015-10-01 00:00:00

abstract：:Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects ac...

journal_title：Drug discovery today

authors： Bauer RA

更新日期：2015-09-01 00:00:00

abstract：:The choroid plexus (CP) is a highly vascularized organ located in the brain ventricles and contains a single epithelial cell layer forming the blood-cerebrospinal fluid barrier (BCSFB). This barrier is crucial for immune surveillance in health and is an underestimated gate for entry of immune cells during numerous inf...

journal_title：Drug discovery today

authors： Demeestere D,Libert C,Vandenbroucke RE

更新日期：2015-08-01 00:00:00

abstract：:Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also pl...

journal_title：Drug discovery today

authors： Kontermann RE,Brinkmann U

更新日期：2015-07-01 00:00:00

abstract：:Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far...

journal_title：Drug discovery today

authors： Kalkman S,van Thiel GJ,Grobbee DE,van Delden JJ

更新日期：2015-07-01 00:00:00

abstract：:The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the rela...

journal_title：Drug discovery today

authors： Jacoby E,Tresadern G,Bembenek S,Wroblowski B,Buyck C,Neefs JM,Rassokhin D,Poncelet A,Hunt J,van Vlijmen H

更新日期：2015-06-01 00:00:00

abstract：:Chronic infection with hepatitis B virus (HBV) often leads to the development of liver cancer and cirrhosis, creating immense sociological, clinical and economic burdens worldwide. Although current anti-HBV medications manage to control the disease progression and help restore normal liver functions, they often fail t...

journal_title：Drug discovery today

authors： Ahmed M,Wang F,Levin A,Le C,Eltayebi Y,Houghton M,Tyrrell L,Barakat K

更新日期：2015-05-01 00:00:00

abstract：:Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal disease that affects primarily older adults. After a decade of negative (or inconsistent) results, two recent clinical trials have demonstrated that slowing disease progression with medication is possible. An improved understanding of di...

journal_title：Drug discovery today

authors： Spagnolo P,Wells AU,Collard HR

更新日期：2015-05-01 00:00:00

abstract：:The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhil...

journal_title：Drug discovery today

authors： Zheng X,Zhang X,Wang G,Hao H

更新日期：2015-05-01 00:00:00

abstract：:Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. An...

journal_title：Drug discovery today

authors： Finley SD,Chu LH,Popel AS

更新日期：2015-02-01 00:00:00

abstract：:For a fortunate subset of pharmaceutical companies, a regulatory approval is the culmination of massive investment in time, work and money. What happens next? Some companies proceed to build a pipeline and obtain additional approvals. Others do not. In this present report, post-approval fate is evaluated and it was fo...

journal_title：Drug discovery today

authors： Kinch MS

更新日期：2015-02-01 00:00:00

abstract：:Here, I provide an overview of the solid-state characteristics, phase transformations and chemical reactions of metoclopramide hydrochloride monohydrate (MCP HCl H2O). Three unique techniques, including thermoanalytical methods, one-step simultaneous differential scanning calorimetry (DSC) and Fourier transform infrar...

journal_title：Drug discovery today

authors： Lin SY

更新日期：2015-02-01 00:00:00

abstract：:Poly(lactic-co-glycolic acid) (PLGA), a US Food and Drug Administration (FDA)-approved copolymer, has been exploited widely in the design of nanoparticles because it is biodegradable, biocompatible, protects the drug molecules from degradation, and aids in producing sustained and targeted delivery. However, certain co...

journal_title：Drug discovery today

authors： Pandita D,Kumar S,Lather V

更新日期：2015-01-01 00:00:00

abstract：:Adverse environmental conditions faced by an individual early during its life, such as gestational hypoxia, can have a profound influence on the risk of diseases, such as neurological disorders, in later life. Clinical and preclinical studies suggest that epigenetic programming of gene expression patterns in response ...

journal_title：Drug discovery today

authors： Ma Q,Xiong F,Zhang L

更新日期：2014-12-01 00:00:00

abstract：:The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studie...

journal_title：Drug discovery today

authors： Castelli M,Clementi N,Sautto GA,Pfaff J,Kahle KM,Barnes T,Doranz BJ,Dal Peraro M,Clementi M,Burioni R,Mancini N

更新日期：2014-12-01 00:00:00

abstract：:Over the past decade, together with the improvement of traditional cancer treatments, conveniently designed (with respect to their size, shape, main material, and coating) and specifically targeted nanovehicles have been developed. Nano-sized carriers can be functionalized to recognize key structures expressed in canc...

journal_title：Drug discovery today

authors： Saenz del Burgo L,Pedraz JL,Orive G

更新日期：2014-10-01 00:00:00

abstract：:In vitro human small intestine models play a crucial part in preclinical drug development. Although conventional 2D systems possess many advantages, such as facile accessibility and high-throughput capability, they can also provide misleading results due to their relatively poor recapitulation of in vivo physiology. S...

journal_title：Drug discovery today

authors： Yu J,Carrier RL,March JC,Griffith LG

更新日期：2014-10-01 00:00:00

abstract：:Allosteric modulators have the potential to fine-tune protein functional activity. Therefore, the targeting of allosteric sites, as a strategy in drug design, is gaining increasing attention. Currently, it is not trivial to find and characterize new allosteric sites by experimental approaches. Alternatively, computati...

journal_title：Drug discovery today

authors： Lu S,Huang W,Zhang J

更新日期：2014-10-01 00:00:00

abstract：:The poor translational validity of autoimmune-mediated inflammatory disease (AIMID) models in inbred and specific pathogen-free (SPF) rodents underlies the high attrition of new treatments for the corresponding human disease. Experimental autoimmune encephalomyelitis (EAE) is a frequently used preclinical AIMID model....

journal_title：Drug discovery today

authors： 't Hart BA,Jagessar SA,Kap YS,Haanstra KG,Philippens IH,Serguera C,Langermans J,Vierboom M

更新日期：2014-09-01 00:00:00

abstract：:Inhibitors of epigenetic targets have entered clinical trials with some success, in particular for combined therapies. Like many other chemotherapeutics these new classes of molecules have dose-limiting toxicities and highly active metabolism in vivo resulting in lower efficacy than expected. This review presents drug...

journal_title：Drug discovery today

authors： el Bahhaj F,Dekker FJ,Martinet N,Bertrand P

更新日期：2014-09-01 00:00:00

abstract：:Drugs targeting infectious diseases have greatly improved public health. A study to evaluate all US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals that the number of new agents targeting infectious disease peaked during the 1990s and declined rapidly thereafter. Molecules targeting b...

journal_title：Drug discovery today

authors： Kinch MS,Patridge E,Plummer M,Hoyer D

更新日期：2014-09-01 00:00:00

abstract：:The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or ...

journal_title：Drug discovery today

authors： Timmins P,Brown J,Meanwell NA,Hanna GJ,Zhu L,Kadow JF

更新日期：2014-09-01 00:00:00

abstract：:The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation, much is needed to ...

journal_title：Drug discovery today

authors： Tuder RM

更新日期：2014-08-01 00:00:00

abstract：:Pulmonary arterial hypertension (PAH) is a progressive disease that involves pathological remodeling, vasoconstriction and thrombosis. Alterations in hemostasis, coagulation and platelet activation are consistently observed in PAH patients. Microparticles derived from platelets, inflammatory cells and the endothelium ...

journal_title：Drug discovery today

authors： Lannan KL,Phipps RP,White RJ

更新日期：2014-08-01 00:00:00

abstract：:Active immunotherapy of neurodegenerative proteinopathies, such as Alzheimer's disease, requires a Th2 antibody immune response with exclusion of damaging inflammatory Th1 immunity. Because these diseases affect the elderly whom, owing to immunosenescence, are frequently immune compromised, a successful therapy would ...

journal_title：Drug discovery today

authors： Marciani DJ

更新日期：2014-07-01 00:00:00

abstract：:Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioava...

journal_title：Drug discovery today

authors： Zhang X,Wu W

更新日期：2014-07-01 00:00:00

abstract：:Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...

journal_title：Drug discovery today

authors： Laurencin CT,Ashe KM,Henry N,Kan HM,Lo KW

更新日期：2014-06-01 00:00:00

abstract：:Manipulation of the human immune system is becoming more of a therapeutic focus as a treatment option or complement. Prominent examples are the increasing use of monoclonal antibodies in combating malignant tumours, and the numerous adoptive immunotherapy trials underway. One important aspect of any use of the human i...

journal_title：Drug discovery today

authors： Gustafsson K,Anderson J,Fisher JPH,Yan M

更新日期：2014-06-01 00:00:00

abstract：:In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput te...

journal_title：Drug discovery today

authors： Khan SR,Baghdasarian A,Fahlman RP,Michail K,Siraki AG

更新日期：2014-05-01 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) is one of the most complex motor neuron diseases. Even though scientific discoveries are accelerating with an unprecedented pace, to date more than 30 clinical trials have ended with failure and staggering frustration. There are too many compounds that increase life span in mice, bu...

journal_title：Drug discovery today

authors： Genç B,Özdinler PH

更新日期：2014-04-01 00:00:00

abstract：:Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% ...

journal_title：Drug discovery today

authors： Bi FC,Frost HN,Ling X,Perry DA,Sakata SK,Bailey S,Fobian YM,Sloan L,Wood A

更新日期：2014-03-01 00:00:00

abstract：:The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation. 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is ...

journal_title：Drug discovery today

authors： Alhouayek M,Masquelier J,Muccioli GG

更新日期：2014-03-01 00:00:00

abstract：:Lipidomics is a rapidly growing technology that can be used in biomedical research to study disease mechanisms, identify novel disease biomarkers and drug efficacy biomarkers, and reveal off-target effects. Lipidomics can also be used to elucidate the mechanism of action of different drug compounds or as readouts in M...

journal_title：Drug discovery today

authors： Vihervaara T,Suoniemi M,Laaksonen R

更新日期：2014-02-01 00:00:00