Abstract：
:Medicinal chemistry makes a vital contribution to small molecule drug discovery, and the quality of it contributes directly to research effectiveness as well as to downstream costs, speed and survival in development. In recent years, the discipline of medicinal chemistry has evolved and witnessed many noteworthy contributions that propose and offer potential improvements to medicinal chemistry practice; however, the impact of these ideas is limited by their acceptance and deployment into every-day activity and, as a result, the quality of medicinal chemistry remains variable. For the good of the industry and the medicinal chemistry discipline, there is a need to move from retrospective learning to prospective control of medicinal chemistry practice to improve cost effectiveness, probability of success and survival rates.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Johnstone Cdoi
10.1016/j.drudis.2012.01.010subject
Has Abstractpub_date
2012-06-01 00:00:00pages
538-43issue
11-12eissn
1359-6446issn
1878-5832pii
S1359-6446(12)00012-8journal_volume
17pub_type
杂志文章abstract：:Model-based drug discovery (MBDDx) aims to build and continuously improve the quantitative understanding of the relation between drug exposure (target engagement) efficacy and safety, to support target validation; to define compound property criteria for lead optimization and safety margins; to set the starting dose; ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.05.012
更新日期：2013-08-01 00:00:00
abstract：:Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu thro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.010
更新日期：2016-07-01 00:00:00
abstract：:Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for pa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.10.013
更新日期：2018-05-01 00:00:00
abstract：:Metabolic determinations are an integral part of every drug-discovery and drug-development program. Recent emphasis has been to increase sample throughput while, at the same time, increase information content within assays. To this end, screening for potential drug-drug interactions, overall metabolic stability and me...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.01.007
更新日期：2007-03-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.04.001
更新日期：2014-08-01 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：:Acute and chronic cough represent one of the most common symptoms of medical importance but effective pharmacotherapy is, to all intents and purposes, absent. Numerous initiatives targeting the recently discovered tussive pathways are in progress. Here, we review the current antitussive armamentarium and provide an up...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.11.004
更新日期：2013-04-01 00:00:00
abstract：:Atrial fibrillation (AF) is the most common cardiac arrhythmia facing physicians, afflicting 13% of men and 11% of women over 85 years of age. Epidemiological studies estimate that there are ≥ 11 million AF sufferers in the seven major economies and that its prevalence will increase two- to threefold over the next 50 ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.007
更新日期：2012-07-01 00:00:00
abstract：:'The climate is perfect for a proactive search for partners between industry and academia.' ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01543-9
更新日期：2000-09-01 00:00:00
abstract：:The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimate...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.07.003
更新日期：2020-09-01 00:00:00
abstract：:Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis. It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent. In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2020.09.001
更新日期：2020-09-09 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.05.012
更新日期：2015-10-01 00:00:00
abstract：:Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from unsatisfactory efficacy owing to fast clearance from the vitreous humour and insufficient distribution into the retina. Engineered nanoparticles have been appli...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.005
更新日期：2019-08-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.07.012
更新日期：2014-10-01 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：:Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a ph...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.012
更新日期：2017-04-01 00:00:00
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 ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.10.009
更新日期：2019-02-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.06.015
更新日期：2015-11-01 00:00:00
abstract：:In therapeutic areas aimed at developing an orally administered drug, the pharmacokinetic profile of a drug candidate after oral administration in vivo is pivotal in evaluating its success. This can be done by monitoring the plasma concentration versus time after dosing and calculating the area under the curve (AUC). ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(98)01299-9
更新日期：1999-05-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.07.003
更新日期：2010-09-01 00:00:00
abstract：:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.01.021
更新日期：2019-03-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.009
更新日期：2008-03-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.09.003
更新日期：2009-12-01 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：:Functional proteomics approaches aim to characterize comprehensively the function of gene products, and provide a first-level understanding of cellular mechanisms. Here, we review recent techniques for the construction and prediction of large-scale protein-interaction networks, with a particular emphasis on computatio...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02281-x
更新日期：2002-06-01 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：:Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (s...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2011.12.006
更新日期：2012-02-01 00:00:00
abstract：:The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer appro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.07.024
更新日期：2007-10-01 00:00:00
abstract：:Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of prot...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.03.017
更新日期：2006-05-01 00:00:00
abstract：:The focus of high-throughput drug discovery has progressed through the genome and the transcriptome and is now moving towards more difficult problems in assessing the proteome, glycome and metabolome. Microarrays are currently the major tool in the assessment of gene expression via cDNA or RNA analysis; however, they ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02773-9
更新日期：2003-07-15 00:00:00
