Abstract:
:The clinical treatment of multifactorial pathologies (e.g. cancer, Alzheimer's disease, psychiatric disorders), is still a major challenge. Many researches have been published dealing with the design of multiple ligands, able to act at the same time towards several targets relevant for a given pathology. In the present review, the clinical results about these compounds have been reported, together with the design strategy adopted, in order to allow a critical evaluation of the outcomes of these efforts. What is emerging is that several effective design strategies of multitarget compounds are available, and the choice among these appears to be dependent on the therapeutic area considered. However, at present, besides multitarget drugs discovered during optimization efforts by means of phenotypic assays, drug coadministrations or fixed dose formulations appear to be more useful therapeutic options than designed multiple ligands; this scenario will change when systems biology will be able to select critical targets, i.e. nodal proteins that should be inhibited in order to obtain a therapeutic action; at this point, the design of multiple ligands will allow a renaissance of medicinal chemistry.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Costantino L,Barlocco Ddoi
10.2174/092986712801215883subject
Has Abstractpub_date
2012-01-01 00:00:00pages
3353-87issue
20eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20120607-3journal_volume
19pub_type
杂志文章,评审abstract::Hereditary amyloidogenic transthyretin (TTR) (ATTR) amyloidosis is an autosomal dominant form of fatal hereditary amyloidosis. Owing to progress in biochemical and molecular genetic analyses, this disease is now believed to occur worldwide. As of today, reports of about 120 different points of single or double mutatio...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712800269317
更新日期:2012-01-01 00:00:00
abstract::Ambient level of gamma -aminobutyric acid (GABA), the major inhibitory neurotransmitter of the brain is mediated by neuronal and glial GABA transporters (GATs), members of the sodium and chloride ion-dependent solute carrier family. The neuronal GABA transporter subtype (GAT-1) has already been proven to be the target...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986710791299939
更新日期:2010-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180214112536
更新日期:2018-01-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must b...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787846587
更新日期:2009-01-01 00:00:00
abstract::Inflammation is a local or systemic tissue reaction caused by external or internal stimuli with the objective to remove the noxa, inhibit its further dissemination and eventually repair damaged tissue. Blood vessels and perivascular connective tissue are important regulators of the inflammatory process. After a short ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709789760751
更新日期:2009-01-01 00:00:00
abstract::To this point, efforts to develop therapeutic peptides for intracellular applications were guided by the perception that unmodified linear peptides are highly unstable and therefore structural modifications are required to reduce proteolytic breakdown. Largely, this concept is a consequence of the fact that most resea...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170508143523
更新日期:2017-01-01 00:00:00
abstract::It is well recognised that increased levels of high density lipoprotein (HDL) protect against atherosclerosis and correlate with improved prognosis for vascular disease associated events. While many of the atheroprotective effects of HDL are ascribed to the ability to remove cholesterol from the vasculature through th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787458425
更新日期:2009-01-01 00:00:00
abstract::Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986711796642599
更新日期:2011-01-01 00:00:00
abstract::O-Prenyl secondary metabolites (3,3-dimethylallyl, geranyl-, farnesyl- and related biosynthetic derivatives) represent a class of rarely occurring natural products. In the last two decades such compounds have been found to exert promising and effective pharmacological activities, mainly in terms of anti-cancer propert...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150716114758
更新日期:2015-01-01 00:00:00
abstract::ATP binding cassette (ABC) transporters are involved in drug absorption, distribution and elimination. They also mediate multidrug resistance in cancer cells. Isoflavones, such as genistein (GNT), belong to a class of naturally-occurring compounds found at high concentrations in commonly consumed soya based-foods and ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160406120711
更新日期:2016-01-01 00:00:00
abstract::The utilization of graphene-based nanomaterials combined with magnetic nanoparticles offers key benefits in the modern biomedicine. In this minireview, we focus on the most recent advances in hybrids of magnetic graphene derivatives for biomedical applications. We initially analyze the several methodologies employed f...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666161216144218
更新日期:2017-01-01 00:00:00
abstract::Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities. Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or be...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320100008
更新日期:2013-01-01 00:00:00
abstract::The neuropeptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems and it is known that after binding to the neurokinin-1 (NK-1) receptors, SP regulates many biological functions in the central nervous system such as emotional behaviour, stress, depression, anxiety, em...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795496746
更新日期:2011-01-01 00:00:00
abstract::ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033368475
更新日期:2003-02-01 00:00:00
abstract::Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160607111806
更新日期:2016-01-01 00:00:00
abstract::This investigation aims to evaluate strategies for an efficient selection of bioactive compounds from the multitude and biodiversity of the plant kingdom. Statistics prove natural products (NPs) as a source leading most consistently to successful development of new drugs. However, there are several reasons why the int...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706777442075
更新日期:2006-01-01 00:00:00
abstract::Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been a global challenge. The complicated forms of the Coronavirus Disease 2019 (COVID-19) can evolve to multiple-organ failure, including several coagulopathies related to a sudden worsening of respiratory status. This article aimed to review s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666201005112231
更新日期:2020-10-05 00:00:00
abstract::The Src family consists of eight non-receptor protein tyrosine kinases characterised by a common structure. Based on their amino acid sequence, Src family kinases are grouped into two subfamilies, which are also characterised by different tissue specificity. Src kinases are involved in signal transduction pathways tri...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784310404
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The sterile alpha motif (Sam) domain is a small helical protein module, able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable target...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666181009114445
更新日期:2020-01-01 00:00:00
abstract::In situ hybridization (ISH) is a type of hybridization that uses a labeled complementary DNA or RNA strand to localize a specific DNA or RNA sequence on a chromosome or section of tissue (in-situ) fixed on a slide. Flourescence in-situ hybridization (FISH) technique facilitates the localization of genes to different c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712801661031
更新日期:2012-01-01 00:00:00
abstract::Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190201142814
更新日期:2020-01-01 00:00:00
abstract::Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the last decades, the precise mechanisms underlying plaque destabilization are still unknown. The disruption of the plaque and the thrombosis in the lumen th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150311150829
更新日期:2015-01-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted from endocrine cells in the gut mucosa in response to meal ingestion. It is an important incretin hormone; mice with a null mutation in the GLP-1 receptor gene develop glucose intolerance. In addition, it inhibits gastrointestinal secretion and moti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-11-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disorder that is believed to have complex genetic and environmental influences in the pathogenesis, but etiologies are unidentified for most patients. Until the major causes are better defined, drug development is directed at downstream pathophysi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140916120118
更新日期:2014-01-01 00:00:00
abstract:: ...
journal_title:Current medicinal chemistry
pub_type: 社论
doi:10.2174/092986732533181024105316
更新日期:2018-01-01 00:00:00
abstract::Advances in combinatorial chemistry, high-throughput screening, and molecular modeling have revolutionized the process of drug discovery in the pharmaceutical industry. Drug discovery efforts for the primary protozoal parasitic diseases of the developing world, malaria, leishmaniasis, and trypanosomiasis, have also be...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867003374615
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:COVID-19 has brought the world to its knees and there is an urgent need for new strategies to identify molecules capable of fighting the pandemic. During the last few decades NMR (Nuclear Magnetic Resonance) spectroscopy has emerged as an intriguing structural biology instrument in the antiviral drug discove...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867328666201228123748
更新日期:2020-12-28 00:00:00
abstract::The arachidonic acid metabolizing enzymes, cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX), are both highly expressed during the carcinogenesis in colons. Cigarette smoking promotes these carcinogenic processes at the early stage during adenoma formation. In this article, the involvement of COX-2 and 5-LOX, along...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160321122431
更新日期:2016-01-01 00:00:00
abstract::Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop d...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180316121015
更新日期:2019-01-01 00:00:00
abstract::HupA is a potent, reversible AChEI, which crosses the blood-brain barrier smoothly, and shows high specificity for AChE with a prolonged biological half-life. It has been approved as the drug for the treatment of AD in China, and marketed in USA as a dietary supplement. HupA has been the subject of investigations by a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456747
更新日期:2003-11-01 00:00:00