Abstract：
:Since being introduced to the field of drug discovery at Zeneca Pharmaceuticals in 1991, it has become apparent to me that a blizzard of revolutionary novel approaches has swept through the pharmaceutical industry. Now, the discovery process has become completely transformed and the race to develop commercially successful drugs is now taking place in a very different realm. Rapid advances in automation, combinatorial chemistry, high-throughput screening (HTS), genomics, proteomics and bioinformatics appear to be principally responsible for driving such a rapidly evolving discovery process. In these exciting times for pharmaceutical R&D, it is a delight for me to take over the Editor's reins of Drug Discovery Today.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Tranter Ddoi
10.1016/s1359-6446(98)01289-6subject
Has Abstractpub_date
1999-01-01 00:00:00pages
1-2issue
1eissn
1359-6446issn
1878-5832pii
S1359644698012896journal_volume
4pub_type
杂志文章abstract：:Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.001
更新日期：2017-06-01 00:00:00
abstract：:Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03383-0
更新日期：2005-03-01 00:00:00
abstract：:Understanding skin metabolism is important when considering drug discovery and safety assessment. This review compares xenobiotic skin metabolism in ex vivo skin to reconstructed human skin and reconstructed human epidermis models, concentrating on phase I and phase II enzymes. Reports on phase I enzymes are more abun...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.002
更新日期：2019-09-01 00:00:00
abstract：:Clear links between cancer and cellular signaling triggered by the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and its cognate ligands (IGF-I and IGF-II) have been reported throughout the past two decades. Experimental results suggest that the pharmaceutical targeting of this signaling pathway could be bene...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03512-9
更新日期：2005-08-01 00:00:00
abstract：:The use of computational filters for excluding supposedly nonspecific and promiscuous compounds from chemical libraries is a controversial issue, because many drugs used in clinics today would never reach the market if these filters were applied. In part, this conflict could be caused by the paradigm: one-drug-one-tar...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.02.004
更新日期：2016-06-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.10.014
更新日期：2014-04-01 00:00:00
abstract：:The eventual candidate drug (CD) is often already synthesized during early drug discovery but not nominated until much later. To facilitate the rapid identification of a potential CD, a thoroughly worked-out CD target profile (CDTP) with criteria acceptable for the disease target product profile (TPP) is required at t...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.03.026
更新日期：2019-06-01 00:00:00
abstract：:An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2017.06.011
更新日期：2017-11-01 00:00:00
abstract：:RNA interference (RNAi) and small-molecule approaches are synergistic on multiple levels, from technology and high-throughput screen development to target identification and functional studies. Here, we describe the RNAi screening platform that we have established and made available to the community through the Drosop...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.10.006
更新日期：2007-01-01 00:00:00
abstract：:Biomedical scientists tend to focus on only a small fraction of the proteins encoded by the human genome despite overwhelming genetic evidence that many understudied proteins are important for human disease. One of the best ways to interrogate the function of a protein and to determine its relevance as a drug target i...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.06.020
更新日期：2019-11-01 00:00:00
abstract：:Novel neuroprotective therapies are desperately needed to improve neuronal recovery after ischemic stroke and extend the therapeutic window or offset some of the adverse effects of tissue-type plasminogen activator (tPA). These advances could provide a more effective and safe therapeutic regimen for patients with isch...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.02.011
更新日期：2018-07-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.02.003
更新日期：2008-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.11.001
更新日期：2014-05-01 00:00:00
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...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.09.020
更新日期：2019-02-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.002
更新日期：2007-12-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.09.010
更新日期：2014-12-01 00:00:00
abstract：:The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry. The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive ch...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.11.010
更新日期：2013-04-01 00:00:00
abstract：:Marketing authorization application dossiers of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009-2010 were compared. We aimed to identify whether any differences existed between ODs and non-ODs in number and type of deficits brought forward during the EMA review,...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.06.012
更新日期：2013-10-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.03.021
更新日期：2014-06-01 00:00:00
abstract：:The proces of piecemeal microautophagy of the nucleus describes the way in which autophagy occurs in the nucleus, a realm of the cell once considered to be off limits for autophagy. ...
journal_title：Drug discovery today
pub_type： 新闻
doi：10.1016/s1359-6446(03)02636-9
更新日期：2003-03-15 00:00:00
abstract：:Chemokines are proinflammatory mediators that primarily control leukocyte migration into selected tissues and upregulation of adhesion receptors. They also have a role in pathological conditions that require neovascularization and are implicated in the suppression of viral replication. By interaction with their respec...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(98)01280-x
更新日期：1999-02-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.03.023
更新日期：2014-09-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.07.004
更新日期：2008-10-01 00:00:00
abstract：:Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03489-6
更新日期：2005-07-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.03.017
更新日期：2014-09-01 00:00:00
abstract：:The advent of multiple high-throughput technologies has brought drug discovery round almost full circle, from pharmacological testing of compounds in vivo to engineered molecular target assays and back to integrated phenotypic screens in cells and organisms. In the past, primary screens to identify new pharmacological...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.04.014
更新日期：2006-06-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.07.005
更新日期：2014-09-01 00:00:00
abstract：:The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and p...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.06.001
更新日期：2017-10-01 00:00:00
abstract：:Neuropathic pain research remains a challenging undertaking owing to: (i) the lack of understanding about the underlying disease processes; and (ii) poor predictive validity of the current models of evoked pain used for the screening of novel compounds. Common consensus is that experimental models replicate symptoms (...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.010
更新日期：2012-08-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disorder among older people. However, no cure or disease-modifying treatments are currently available, and the molecular and cellular mechanisms responsible for the etiology of AD remain under debate. Recent studies suggest that the immune system has a cruc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.07.020
更新日期：2013-12-01 00:00:00
