Abstract：
:Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we use historical market data relating to pharmacokinetic (PK), pharmacodynamic (PD), and other drug-related properties to investigate which derivatives within certain drug classes have been most successful on the market. Based on our investigations, we suggest naming the most successful drugs 'overtaking innovation', because they often exceed the market share of all the other derivatives. Seven drug classes showed that the overtaking innovation is never a radical innovation, but rather an early incremental innovation, with advantages in manageability and/or tolerance.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Alt S,Helmstädter Adoi
10.1016/j.drudis.2017.09.009subject
Has Abstractpub_date
2018-02-01 00:00:00pages
208-212issue
2eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30354-9journal_volume
23pub_type
杂志文章,评审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：:Regenerative approaches are promising avenues to effectively cure diseases rather than merely treating symptoms, but are associated with concerns around proliferation in other organs. Given that targeted delivery holds the promise of delivering a drug precisely to its desired site of action, usually with the prospect ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.12.004
更新日期：2017-06-01 00:00:00
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 contr...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.01.010
更新日期：2012-06-01 00:00:00
abstract：:The concept of drug-target residence time has been in focus in recent drug discovery literature. However, few studies consider the combined effect of pharmacokinetics (PK) and binding kinetics (BK) on the duration of effect of a drug. Using a simple model that takes both PK and BK into account, we found that prolongat...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.02.010
更新日期：2013-08-01 00:00:00
abstract：:Effective direct inhibition of adhesion receptors by small molecules has been hampered by extended receptor-ligand interfaces as well as the entropic penalties often associated with inhibition of cell adhesion. Therefore, alternative strategies have targeted enzymes that are centrally involved in the biosynthesis of r...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01581-6
更新日期：2001-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.11.007
更新日期：2008-04-01 00:00:00
abstract：:After years of hesitation a larger number of pharmaceutical and biotech companies are now supporting the idea of a more individualized pharmacotherapy. The companies that are now involved in this research-demanding area will have to face several challenges. The key factor for success will be an in-depth molecular unde...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.09.010
更新日期：2011-10-01 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：: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：:For several decades, the pharmaceutical industry has suffered due to major issues such as reductions of the number of FDA approved drugs and biologics. Several analyses have been highlighted that the 'druglikeness' is one of the strategies to improve succeed rates of screening such as, for instance, high-throughput sc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.01.005
更新日期：2016-04-01 00:00:00
abstract：:Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.01.006
更新日期：2017-06-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.09.001
更新日期：2016-01-01 00:00:00
abstract：:Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.07.012
更新日期：2013-01-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.09.014
更新日期：2009-12-01 00:00:00
abstract：:The global burden of herpes simplex virus (HSV) legitimates the critical need to develop new prevention strategies, such as drugs and vaccines that are able to fight either primary HSV infections or reactivations. Moreover, the ever-growing number of patients receiving transplants increases the number of severe HSV in...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.03.003
更新日期：2016-04-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.03.012
更新日期：2009-06-01 00:00:00
abstract：:There is currently a marketed drug for nearly every nuclear receptor for which the natural ligand has been identified. However, because of the complexity of signal transduction by this class of ligand-regulated transcription factors, few of these drugs have been optimized for pharmaceutical effectiveness. Over the pas...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03201-5
更新日期：2004-09-01 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
abstract：:There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges neede...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.023
更新日期：2016-10-01 00:00:00
abstract：:Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the in...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.017
更新日期：2017-06-01 00:00:00
abstract：:Thermodynamic profiles of ligand binding, particularly enthalpically favored binding signatures, have been suggested as a criterion to support the decision-making process around which compounds to select for further optimization in drug development. The concept was enthusiastically taken up, but turned out to be too s...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.01.014
更新日期：2019-04-01 00:00:00
abstract：:Cocaine is a major drug of abuse whose devastating effects have captured the attention of health officials and policy makers. Based upon the alarming health and crime-related costs associated with the use of this powerful reinforcing drug, immediate therapies are needed for the treatment of cocaine addiction. In this ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(99)01332-x
更新日期：1999-07-01 00:00:00
abstract：:The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.017
更新日期：2016-10-01 00:00:00
abstract：:Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.09.010
更新日期：2006-11-01 00:00:00
abstract：:Hydrocarbon stapling could enable peptides from the key domains of natural proteins to be used therapeutically. Using the technique on a peptide involved in apoptosis, researchers have succeeded in destroying cancer cells in a mouse model of leukaemia. ...
journal_title：Drug discovery today
pub_type： 新闻
doi：10.1016/S1359-6446(04)03268-4
更新日期：2004-11-01 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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.07.008
更新日期：2008-11-01 00:00:00
abstract：:Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.08.002
更新日期：2012-01-01 00:00:00
abstract：:Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.03.015
更新日期：2017-07-01 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：: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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.08.011
更新日期：2007-10-01 00:00:00
