abstract：:The blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such...

journal_title：Drug discovery today

authors： Paolino D,Cosco D,Molinaro R,Celia C,Fresta M

更新日期：2011-04-01 00:00:00

abstract：:Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small mole...

journal_title：Drug discovery today

authors： Verkaar F,Zaman GJ

更新日期：2011-01-01 00:00:00

abstract：:Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...

journal_title：Drug discovery today

authors： Kota SK,Balasubramanian S

更新日期：2010-09-01 00:00:00

abstract：:Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we de...

journal_title：Drug discovery today

authors： Orita M,Moritomo A,Niimi T,Ohno K

更新日期：2010-05-01 00:00:00

abstract：:High-information screening formats, using more physiologically relevant cellular models and readout approaches, are slowly replacing traditional, target-orientated approaches in drug discovery programs. With improved access to primary cells, as well as label-free, non-intrusive methods of compound interrogation (such ...

journal_title：Drug discovery today

authors： Möller C,Slack M

更新日期：2010-05-01 00:00:00

abstract：:The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential s...

journal_title：Drug discovery today

authors： Rivolta MN

更新日期：2010-04-01 00:00:00

abstract：:The emergence of induced pluripotent stem (iPS) cell technology has shifted gene correction therapy toward reality. Crucial issues are ensuring the safety of using iPS cell technology in patients and discovering how best to transfer genetically manipulated iPS cells back into patients. One key issue that has hindered ...

journal_title：Drug discovery today

authors： Nakayama M

更新日期：2010-03-01 00:00:00

abstract：:Epigenetic covalent modifications of DNA and chromatin proteins strongly affect gene expression and cellular activity, and epigenetic misregulation occurs in several diseases, especially cancer. First-generation drugs targeting the relatively promiscuous DNA methylation and histone acetylation modifiers have had succe...

journal_title：Drug discovery today

authors： Best JD,Carey N

更新日期：2010-01-01 00:00:00

abstract：:This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have ...

journal_title：Drug discovery today

authors： van Rijt SH,Sadler PJ

更新日期：2009-12-01 00:00:00

abstract：:Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as 'endocannabinoids' or ...

journal_title：Drug discovery today

authors： Pillarisetti S,Alexander CW,Khanna I

更新日期：2009-12-01 00:00:00

abstract：:When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...

journal_title：Drug discovery today

authors： Bornstein GG,Klakamp SL,Andrews L,Boyle WJ,Tabrizi M

更新日期：2009-12-01 00:00:00

abstract：:Post-translational modifications, such as acetylation or phosphorylation, play a crucial role in the regulation of gene transcription in eukaryotes. Different subtypes of histone acetyl transferases (HATs) catalyze the acetylation of histones on specific lysine residues. A potential role of HATs in the pathology of ca...

journal_title：Drug discovery today

authors： Dekker FJ,Haisma HJ

更新日期：2009-10-01 00:00:00

abstract：:Pharmacological modulation of intracellular cyclic AMP (cAMP) signalling could provide new therapeutic and experimental tools. Although drugs interfering with this pathway have traditionally targeted membrane receptors, the effector enzyme adenylyl cyclase (AC), which functions as a signalling catalyst, also presents ...

journal_title：Drug discovery today

authors： Pavan B,Biondi C,Dalpiaz A

更新日期：2009-10-01 00:00:00

abstract：:A more complete understanding of the mechanisms that drive autoimmune diseases has begun to be translated into therapeutic options with significant clinical consequences. A clear example of this is the introduction of biological therapies, which have provided new therapeutic avenues, as well as validated the mediators...

journal_title：Drug discovery today

authors： Balagué C,Kunkel SL,Godessart N

更新日期：2009-10-01 00:00:00

abstract：:The biopharmaceutical industry is characterized by intense competition, high uncertainty, and strong dependence on scientific knowledge. We show that in order to succeed in this industry, firms need to be positioned along three strategic dimensions: the level of inter-firm R&D partnering, the level of diversification,...

journal_title：Drug discovery today

authors： Erden Z,von Krogh G,Nytorp C,Hultberg M

更新日期：2009-08-01 00:00:00

abstract：:For the past decade, the development of genomic technology has revolutionized modern biological research and drug discovery. Functional genomic analyses enable biologists to perform analysis of genetic events on a global scale and they have been widely used in gene discovery, biomarker determination, disease classific...

journal_title：Drug discovery today

authors： Chen X,Jorgenson E,Cheung ST

更新日期：2009-08-01 00:00:00

abstract：:Immunoinformatics has recently emerged as a critical field for accelerating immunology research. Although still an evolving process, computational models now play instrumental roles, not only in directing the selection of key experiments, but also in the formulation of new testable hypotheses through detailed analysis...

journal_title：Drug discovery today

authors： Tong JC,Ren EC

更新日期：2009-07-01 00:00:00

abstract：:Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of ...

journal_title：Drug discovery today

authors： Ma XH,Zheng CJ,Han LY,Xie B,Jia J,Cao ZW,Li YX,Chen YZ

更新日期：2009-06-01 00:00:00

abstract：:Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. The impressive clinical effectiveness of cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt...

journal_title：Drug discovery today

authors： Alama A,Tasso B,Novelli F,Sparatore F

更新日期：2009-05-01 00:00:00

abstract：:We have broken old surviving dogmas and concepts used in computational chemistry and created an efficient in silico ADME-T pharmacological properties modeling and prediction toolbox for any xenobiotic. With the help of an innovative and pragmatic approach combining various in silico techniques, like molecular modeling...

journal_title：Drug discovery today

authors： Jacob A,Pratuangdejkul J,Buffet S,Launay JM,Manivet P

更新日期：2009-04-01 00:00:00

abstract：:Pulmonary arterial hypertension (PAH) has evolved from an untreatable condition to a disease for which several classes of drugs have now been approved, including various prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Because the pathogenesis of pulmonary hypertension is increasingly u...

journal_title：Drug discovery today

authors： Olsson KM,Hoeper MM

更新日期：2009-03-01 00:00:00

abstract：:Successful strategies for the development of monoclonal antibodies require integration of knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, Fc domain engineering, PK/PD properties and antibody cross-reactivity across species from the early stages of anti...

journal_title：Drug discovery today

authors： Tabrizi MA,Bornstein GG,Klakamp SL,Drake A,Knight R,Roskos L

更新日期：2009-03-01 00:00:00

abstract：:For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...

journal_title：Drug discovery today

authors： Kong DX,Li XJ,Zhang HY

更新日期：2009-02-01 00:00:00

abstract：:One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood-brain barrier (BBB) using transvascular routes following intravenous administration. The dev...

journal_title：Drug discovery today

authors： Juillerat-Jeanneret L

更新日期：2008-12-01 00:00:00

abstract：:With a productivity gap in pharmaceutical research and development, and increased industrialization in both areas, an increased need for precise indicators of productivity has emerged. Measuring scientists' performance can impact the way the tasks are performed and the level of motivation of an individual. This is a c...

journal_title：Drug discovery today

authors： Ullman F,Boutellier R

更新日期：2008-11-01 00:00:00

abstract：:Using a biologically relevant peptide or protein structure as a starting point for lead identification represents one of the most powerful approaches in modern drug discovery. Here, we focus on the protein epitope mimetic (PEM) approach, where folded 3D structures of peptides and proteins are taken as starting points ...

journal_title：Drug discovery today

authors： Robinson JA,Demarco S,Gombert F,Moehle K,Obrecht D

更新日期：2008-11-01 00:00:00

abstract：:A drug molecule should bind to its target with high affinity and selectivity. Because the binding affinity is a combined function of the binding enthalpy and the binding entropy, extremely high affinity requires that both terms contribute favorably to binding. The binding enthalpy, however, is notoriously more difficu...

journal_title：Drug discovery today

authors： Freire E

更新日期：2008-10-01 00:00:00

abstract：:Natural products have been the single most productive source of leads for the development of drugs. Over a 100 new products are in clinical development, particularly as anti-cancer agents and anti-infectives. Application of molecular biological techniques is increasing the availability of novel compounds that can be c...

journal_title：Drug discovery today

authors： Harvey AL

更新日期：2008-10-01 00:00:00

abstract：:The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...

journal_title：Drug discovery today

authors： Farrell EK,Merkler DJ

更新日期：2008-07-01 00:00:00

abstract：:Chemokine receptors control and mediate a diverse array of physiological and pathogenic processes. Many seven transmembrane (TM) G-protein-coupled receptors (GPCRs), including chemokine receptors, exist as homo- or heterodimers. Growing evidence indicates that the dimeric form is the basic functional structure of thes...

journal_title：Drug discovery today

authors： Wang J,Norcross M

更新日期：2008-07-01 00:00:00

abstract：:By the end of 2006, compared with 28% coverage for adults, only 15% of children with HIV that needed antiretroviral treatment were receiving it. Major challenges in delivering treatment include the lack of paediatric antiretrovirals that can be dosed in small children and limited studies examining safety and efficacy ...

journal_title：Drug discovery today

authors： Bowen A,Palasanthiran P,Sohn AH

更新日期：2008-06-01 00:00:00

abstract：:Recent failures in efforts to develop an effective vaccine against HIV-1 infection have emphasized the importance of antiretroviral therapy in treating HIV-1-infected patients. Thus far, inhibitors of two viral enzymes, reverse transcriptase and protease, have had a profoundly positive impact on the survival of HIV-1-...

journal_title：Drug discovery today

authors： Adamson CS,Freed EO

更新日期：2008-05-01 00:00:00

abstract：:The concept of drug-likeness helps to optimise pharmacokinetic and pharmaceutical properties, for example, solubility, chemical stability, bioavailability and distribution profile. A number of molecular descriptors have emerged as reasonably informative and predictive, for example, the Rule-of-Five. Here, we review so...

journal_title：Drug discovery today

authors： Vistoli G,Pedretti A,Testa B

更新日期：2008-04-01 00:00:00

abstract：:Described in this article are strategies implemented to increase the throughput of in vivo rodent pharmacokinetic (PK) studies using the snapshot PK study design and automated methods for compound submission, sample processing, data analysis and reporting. Applying snapshot PK studies to categorize the oral exposure o...

journal_title：Drug discovery today

authors： Liu B,Chang J,Gordon WP,Isbell J,Zhou Y,Tuntland T

更新日期：2008-04-01 00:00:00

abstract：:Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage. ...

journal_title：Drug discovery today

authors： Petersen TK,Sørensen P

更新日期：2008-03-01 00:00:00

abstract：:The eye is afflicted by chronic vision debilitating neovascular disorders, such as age-related macular degeneration, proliferative diabetic retinopathy, and corneal angiogenesis. Photodynamic therapy (PDT) is an innovative, evolving approach for treating neovascular diseases of the eye. PDT refers to the process of ac...

journal_title：Drug discovery today

authors： Christie JG,Kompella UB

更新日期：2008-02-01 00:00:00

abstract：:Three-dimensional (3D) pharmacophore modeling is a technique for describing the interaction of a small molecule ligand with a macromolecular target. Since chemical features in a pharmacophore model are well known and highly transparent for medicinal chemists, these models are intuitively understandable and have been i...

journal_title：Drug discovery today

authors： Wolber G,Seidel T,Bendix F,Langer T

更新日期：2008-01-01 00:00:00

abstract：:Lack of predictability of clinical efficacy and safety is an important problem facing pharmaceutical research today. Translational PK-PD has the ability to integrate data generated from diverse test platforms during discovery and development in a mechanistic framework. Therefore, successful implementation of translati...

journal_title：Drug discovery today

authors： Agoram BM,Martin SW,van der Graaf PH

更新日期：2007-12-01 00:00:00

abstract：:Decisions in drug development are made on the basis of determinations of cause and effect from experimental observations that span drug development phases. Despite advances in our powers of observation, the ability to determine compound mechanisms from large-scale multi-omic technologies continues to be a major bottle...

journal_title：Drug discovery today

authors： Pitluk Z,Khalil I

更新日期：2007-11-01 00:00:00

abstract：:Medical oncologists are increasingly using anti-angiogenic drugs, but identifying the best-suited drug and the optimal dosage and schedule for treatment of patients remain challenging issues. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) are modulated in a variety of diseases incl...

journal_title：Drug discovery today

authors： Bertolini F,Mancuso P,Shaked Y,Kerbel RS

更新日期：2007-10-01 00:00:00