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 development of BBB targeting technologies is a very active field of research and development. One goal is to develop chemically modified derivatives of drugs or chemically modified nanoparticulate vectors of drugs, capable of crossing biological barriers, in particular the BBB. This manuscript will review the approaches that have been explored to achieve these goals, using chemical functionalization of drugs or of drug vector systems and endogenous transporters at the BBB.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Juillerat-Jeanneret Ldoi
10.1016/j.drudis.2008.09.005subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1099-106issue
23-24eissn
1359-6446issn
1878-5832pii
S1359-6446(08)00330-9journal_volume
13pub_type
杂志文章,评审abstract：:The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation, much is needed to ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.05.022
更新日期：2014-08-01 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：: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
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2008.07.002
更新日期：2009-02-01 00:00:00
abstract：:Over the past three decades, statins have become the cornerstone of prevention and treatment of atherosclerotic cardiovascular and metabolic diseases. Albeit generally well tolerated, these drugs can elicit a variety of muscle-associated symptoms that represent the most important reason for treatment discontinuation. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.09.001
更新日期：2017-01-01 00:00:00
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 ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.09.009
更新日期：2018-02-01 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：: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
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.12.003
更新日期：2009-03-01 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：: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：:Healthcare systems are faced with the challenge of providing innovative treatments, while shouldering high drug costs that pharmaceutical companies justify by the high costs of R&D. An emergent technology that could transform R&D efficiency is organ-on-a-chip. The technology bridges the gap between preclinical testing...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.003
更新日期：2019-09-01 00:00:00
abstract：:The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.021
更新日期：2019-12-01 00:00:00
abstract：:Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenome...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02567-9
更新日期：2003-02-15 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(01)01831-1
更新日期：2001-07-01 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
pub_type： 杂志文章
doi：10.1016/j.drudis.2010.03.003
更新日期：2010-05-01 00:00:00
abstract：:Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.04.005
更新日期：2016-08-01 00:00:00
abstract：:To enable the list of genes and proteins contained within genomic databases to be useful for drug discovery, we need to understand how the genome maps into the phenome. An essential, but not explicitly listed ingredient of the genome is the regulatory interactions between genes and proteins that form a genome-wide net...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02463-7
更新日期：2002-10-15 00:00:00
abstract：:Many of the drug candidates that fail in clinical trials are withdrawn because of unforeseen effects of human metabolism, such as toxicity and unfavorable pharmacokinetic profiles. Early pre-clinical elimination of such compounds is important but not yet possible. An ideal system would enable researchers to make a con...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(03)02971-4
更新日期：2004-02-01 00:00:00
abstract：:Advanced chemotherapy fails to treat liver cancer but recent progress in understanding epigenetic modifications have witnessed promising clinical outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding histone proteins) without changing the DNA sequence. Such epigenetic mechanisms include histone ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.07.008
更新日期：2017-11-01 00:00:00
abstract：:Psoriasis is a chronic autoimmune skin disorder triggered by either genetic factors, environmental factors, life style, or a combination thereof. Clinical investigations have identified pathogenesis, such as T cell and cytokine-mediated, genetic disposition, antimicrobial peptides, lipocalin-2, galectin-3, vaspin, fra...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.09.023
更新日期：2020-12-01 00:00:00
abstract：:Telomerase is a ribonucleic reverse transcriptase enzyme that uses an integral RNA component as a template to add tandem telomeric DNA repeats, TTAGGG, at the 3' end of the chromosomes. 85-90% of human tumors and their derived cell lines predominantly express high levels of telomerase, therefore contributing to cancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.015
更新日期：2019-07-01 00:00:00
abstract：:Osteoarthritis (OA), the most common and disabling form of arthritic disease, is characterized by a slow and progressive degeneration of articular cartilage. Its etiology is multifactorial and includes genetic predisposition, obesity and aging. In addition to the cartilage itself, OA also involves the surrounding tiss...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.01.004
更新日期：2011-05-01 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：: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：: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：:For a fortunate subset of pharmaceutical companies, a regulatory approval is the culmination of massive investment in time, work and money. What happens next? Some companies proceed to build a pipeline and obtain additional approvals. Others do not. In this present report, post-approval fate is evaluated and it was fo...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.10.013
更新日期：2015-02-01 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 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：:Many pharmaceutical companies aim to reduce reactive metabolite formation by chemical modification at early stages of drug discovery. A practice often applied is the detection of stable trapping products of electrophilic intermediates with nucleophilic trapping reagents to guide rational structure-based drug design. T...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.018
更新日期：2017-05-01 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
abstract：:It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. Ho...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.10.021
更新日期：2018-02-01 00:00:00
