Abstract:
:There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of these immunotherapies is summarized. Immunoinformatic approaches look promising to unfold this potential, although still unstable and difficult to interpret. Animal models have progressed a great deal in recent years, finally narrowing the gap from bench to bedside. However, translation to the clinic should be done with precaution. The most significant results concerning clinical benefit might come from detailed immunologic investigations made during well designed clinical trials of dendritic-cell-based therapies, which in general prove safe.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Imhof M,Karas I,Gomez I,Eger A,Imhof Mdoi
10.1016/j.drudis.2012.07.010subject
Has Abstractpub_date
2013-01-01 00:00:00pages
35-42issue
1-2eissn
1359-6446issn
1878-5832pii
S1359-6446(12)00264-4journal_volume
18pub_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::Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.020
更新日期:2017-07-01 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::In the past five years therapeutic monoclonal antibodies have established themselves as perhaps the most important and rapidly expanding class of therapeutic drugs. More than 25% of pharmacological agents that are currently under development are based on antibodies and the total income generated from them in 2002 exce...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02714-4
更新日期:2003-06-01 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::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
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.07.012
更新日期:2015-11-01 00:00:00
abstract::The Discussion Forum provides a medium for airing your views on any issues related to the pharmaceutical industry and obtaining feedback and discussion on these views from others in the field. You can discuss issues that get you hot under the collar, practical problems at the bench, recently published literature, or j...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)01816-5
更新日期:2001-06-01 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
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.03.005
更新日期:2015-07-01 00:00:00
abstract::Gene expression microarrays have been used widely to address increasingly complex biological questions and to produce an unprecedented amount of data, but have yet to realize their full potential. The interpretation of microarray data remains a major challenge because of the complexity of the underlying biological net...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03565-8
更新日期:2005-09-01 00:00:00
abstract::Rab GTPases constitute the largest family of small GTPases. Rabs regulate not only membrane trafficking but also cell signaling, growth and survival, and development. Increasingly, Rabs and their effectors are shown to be overexpressed or subject to loss-of-function mutations in a variety of disease settings, includin...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.03.012
更新日期:2017-08-01 00:00:00
abstract::To date, the life sciences 'omics' revolution has not lived up to the expectation of boosting the drug discovery process. The major obstacle is dealing with the volume and diversity of data generated. An enhanced-science (e-science) approach based on remote collaboration, reuse of data and methods, and supported by a ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03680-9
更新日期:2006-03-01 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
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.07.005
更新日期:2008-10-01 00:00:00
abstract::The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.01.001
更新日期:2013-06-01 00:00:00
abstract::Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches imple...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.09.004
更新日期:2013-01-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01674-3
更新日期:2001-03-01 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 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
pub_type: 杂志文章
doi:10.1016/j.drudis.2009.04.004
更新日期:2009-08-01 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
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...
journal_title:Drug discovery today
pub_type:
doi:10.1016/j.drudis.2013.08.003
更新日期:2013-12-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01551-8
更新日期:2000-09-01 00:00:00
abstract::Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.02.004
更新日期:2017-07-01 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::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::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01619-6
更新日期:2001-02-01 00:00:00
abstract::The recent increase in pharmaceutical companies' efforts toward the treatment of obesity reflects recognition of the related health risks, the growth of knowledge about mechanisms that control energy balance, and the potential market for new compounds. The current patent literature gives a picture of the targets that ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03244-1
更新日期:2004-10-15 00:00:00
abstract::Novel starting points for drug discovery projects are generally found either by screening large collections of compounds or smaller more-focused libraries. Ideally, hundreds or even thousands of actives are initially found, and these need to be reduced to a handful of promising lead series. In several sequential steps...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03703-7
更新日期:2006-01-01 00:00:00
abstract::In developed countries that protect core aspects of the fundamental human right to the highest attainable standard of health, how does that right intersect with intellectual property rights? Here, the human rights implication of providing access to all cancer drugs recommended by experts in a developed country is cons...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.04.009
更新日期:2020-07-01 00:00:00
abstract::3D bioprinting has emerged as the intersection between chemistry, biology and technology. Through its integration of cells, biocompatible materials and robotic-controlled dispensing systems, the process enables the production of structures that are biomimetic and functional, thus revolutionizing the concept of tissue ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.09.012
更新日期:2019-01-01 00:00:00
abstract::Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.01.019
更新日期:2012-03-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.004
更新日期:2019-11-01 00:00:00