Abstract:
:A large number of human disorders are caused by defects in protein folding resulting from genetic mutations or adverse physiological conditions, and these are collectively referred to protein misfolding diseases. Such disorders imply dysfunction of a cellular process either as a result of a toxic gain of function due to protein aggregation, or loss of function due to protein instability, inefficient folding or defective trafficking. For a number of cases, drugs acting directly on the affected protein have been found to prevent misfolding and rescue function. This brief review will illustrate molecular mechanisms through which small molecules acting as folding correctors can prevent excessive protein buildup or recover faulty protein conformers, thus acting as effective therapeutic pharmacological chaperones. As background, the principles underlying the thermodynamics and kinetics of the protein folding reaction will be overviewed, as well as pathways leading to the formation of misfolding. The mechanism of action of small molecule correctors will then be discussed in light of these basic principles using illustrative examples referring to drugs that are effective over proteins involved in trafficking and folding diseases, amyloid aggregation disorders and metabolic deficiencies. An outlook on synergistic effects between different folding correctors and their combination with proteostasis regulators will also be addressed, as a relevant strategy towards the design of more effective therapies against protein folding diseases.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Gomes CMdoi
10.2174/1568026611212220002subject
Has Abstractpub_date
2012-01-01 00:00:00pages
2460-9issue
22eissn
1568-0266issn
1873-4294pii
CTMC-EPUB-20130104-2journal_volume
12pub_type
杂志文章,评审abstract::Safety and biocompatibility assessment of biomaterials are themes of constant concern as advanced materials enter the market as well as products manufactured by new techniques emerge. Within this context, this review provides an up-to-date approach on current methods for the characterization and safety assessment of b...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180410151518
更新日期:2018-01-01 00:00:00
abstract::The gradual alignment with all of drug metabolism with all aspects of drug discovery and development has led to a complete realignment of the way the work is conducted. From a background of conducting bespoke in vivo studies much of the work is now in a high throughput screening mode. Large technological advances have...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611794480909
更新日期:2011-01-01 00:00:00
abstract::Machine learning (ML) computational methods for predicting compounds with pharmacological activity, specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties are being increasingly applied in drug discovery and evaluation. Recently, machine learning techniques such as...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026614666140929124203
更新日期:2014-01-01 00:00:00
abstract::Iron chelators may be of value as therapeutic agents in the treatment of cancer. They may act by depleting iron, a necessary nutrient, and limiting tumor growth. Alternatively or additionally, they may form redox-active metal complexes that cause oxidative stress via production of reactive oxygen species, damaging cri...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043387269
更新日期:2004-01-01 00:00:00
abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/156802661911190725100827
更新日期:2019-01-01 00:00:00
abstract::An evaluation of existing and proposed Fe chelators, both synthetic and natural products, for the treatment of Fe-overload disease must address a number of issues. There are fundamental parameters that determine the efficacy of a drug: absorption, distribution, metabolism, clearance and toxicity. However, the administ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611794785163
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:The impact of fungal infections on human health has increased considerably within a past few decades. Although drugs with antifungal properties are available, but they are less effective and are associated with side effects. OBJECTIVE AND METHOD:To screen the bacterial isolates from Sesamum indicum and to i...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026618666180206102140
更新日期:2018-01-01 00:00:00
abstract::Liver cancer is the fifth (6.3% of all cancers i.e., 548,000 cases/year) and ninth (2.8% of all cancers i.e., 244,000 cases/year) most prevalent cancer worldwide in men and women, respectively. Although multiple choices of therapies are offered for Hepatocellular Carcinoma (HCC) like liver resection or transplant, rad...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026619666191114113048
更新日期:2020-01-01 00:00:00
abstract::Low drug productivity has been a significant problem of the pharmaceutical industry for several decades even though numerous novel technologies were introduced during this period. Currently pharmacologic dogma, "single drug, single target, single disease", is at the root of the lack of drug productivity. From a system...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026616666160530181328
更新日期:2016-01-01 00:00:00
abstract::Although water molecules are small and only consist of two different atom types, they play various roles in cellular systems. This review discusses their influence on the binding process between biomacromolecular targets and small molecule ligands and how this influence can be modeled in computational drug design appr...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610790232288
更新日期:2010-01-01 00:00:00
abstract::There exists a huge attrition rate of molecules in clinical trials. It was expected that high-throughput screening and combinatorial chemistry would make the task of producing drugs easier. However, the efforts of the past decade have not been an unvarnished success. As a result, a lot of experimental and computationa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392968
更新日期:2002-12-01 00:00:00
abstract::Chemical genomics combines chemistry with molecular biology as a means of exploring the function of unknown proteins or identifying the proteins responsible for a particular phenotype induced by a small cell-permeable bioactive molecule. Chemical genomics therefore has the potential to identify and validate therapeuti...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612801319025
更新日期:2012-01-01 00:00:00
abstract::Errors in the mitotic process are thought to be one of the principal sources of the genetic instability that hallmarks cancer. Unsurprisingly, many of the proteins that regulate mitosis are aberrantly expressed in tumour cells when compared to their normal counterparts. These may represent a good source of targets for...
journal_title:Current topics in medicinal chemistry
pub_type: 更正并重新发布的文章,杂志文章,评审
doi:10.2174/1568026054637719
更新日期:2005-01-01 00:00:00
abstract:AIMS:The need to find new antimicrobial agents to cope with this phenomenon increases. BACKGROUND:Infection diseases are illness caused by different microorganisms, such as bacteria, among those caused by resistant bacteria are associated with greater morbidity, mortality and cost of the treatment than those caused by...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026619666191121123926
更新日期:2020-01-01 00:00:00
abstract::At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection. While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation. With the onset of bacterial drug resistan...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313040008
更新日期:2013-01-01 00:00:00
abstract::The pharmacophore modeling in modern drug research has been applied for both bioactivity profiling and early stage of risk assessment of potential side effects and toxicity due to interactions of drug candidates with antitargets namely P-glycoprotein, hERG, cytochrome P450 and pregnane X-receptor. In this article, an ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313090004
更新日期:2013-01-01 00:00:00
abstract::Ischemic heart disease and cerebrovascular disease are the leading causes of death in the world. Surprisingly, these diseases are treated by relatively antiquated drugs. However, due to our improved understanding of the underlying pathology of these diseases, and a number of technological advances in tools for drug di...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026013395380
更新日期:2001-06-01 00:00:00
abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/1568026619666181120121528
更新日期:2018-01-01 00:00:00
abstract::The conventional way of characterizing a disease consists of correlating clinical symptoms with pathological findings. Although this approach for many years has assisted clinicians in establishing syndromic patterns for pathophenotypes, it has major limitations as it does not consider preclinical disease states and is...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666181025113226
更新日期:2018-01-01 00:00:00
abstract::Post translational modification (PTM) is one of the critical levels in regulation of gene expression that determines the fate of proteins after translation in eukaryotic cells. Since the detection of PTM sites in proteins is useful for diagnosis and prevention of diseases, numerous web-tool predictors are introduced t...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170328100908
更新日期:2017-01-01 00:00:00
abstract::A modified version of the CORAL software (http://www.insilico.eu/coral) allows building up the classification model for the case of the Yes/No data on the anti-sarcoma activity of organic compounds. Three random splits into the sub-training, calibration, and test sets of the data for 3017 compounds were examined. The ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026611212240004
更新日期:2012-01-01 00:00:00
abstract::Angiotensin II (AII), Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, the primary active hormone of the Renin-Angiotensin-System (RAS), is a major vasoconstrictor implicated in the cause of hypertension. To unravel the question of the biologically active conformation(s) of this flexible peptide hormone and to better understa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451375
更新日期:2004-01-01 00:00:00
abstract::In the late 1970s and the early 1980s the initial p38 chemotype, the triaryl imidazoles, was discovered as an off-target effect during the development of cyclooxygenase and 5-lipoxygenase inhibitors long before the identity of the p38 kinase was known. During the last 10 years a number of novel p38 chemotypes were dis...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026054985948
更新日期:2005-01-01 00:00:00
abstract::Several strategies used in the rational design and synthesis of fluorinated compounds as potential therapeutic agents are reviewed. Applications of fluorine substitution in empirical SAR studies for lead development also are discussed, along with the implications with respect to fluorine target interactions that can b...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606777951073
更新日期:2006-01-01 00:00:00
abstract::Diabetes mellitus type 2 (DMT2) is a metabolic disease characterized by a chronic increase in glycemia that promotes several long-term complications and high mortality. Some enzymes involved in glycaemic control, such as α -(1,4)-glucosidase, have now been established as novel pharmacological targets. Coumarins have s...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026619666181130113033
更新日期:2018-01-01 00:00:00
abstract::Neural activity utilizes energy resources and requires replenishment of metabolites through vascular dilation. During wake, cortical neurons usually have depolarized membrane potentials and exhibit frequent spontaneous action potentials, requiring an increased metabolic delivery to activated tissue and causing blood v...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611797470349
更新日期:2011-01-01 00:00:00
abstract::The low affinity A(2B) adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various speci...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026033392264
更新日期:2003-01-01 00:00:00
abstract::Since the histamine-3 receptor (H₃R) was cloned in 1999, huge efforts have been made by most of the key players in the pharmaceutical industry as well as in smaller biotech companies to increase the knowledge on this peculiar receptor, with the ultimate goal of bringing new drugs to the market. This review gives a sur...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611795860906
更新日期:2011-01-01 00:00:00
abstract::Cardiac fibrosis is associated with most cardiac diseases. Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts. Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells. Myofibroblasts are hardly present in...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313030005
更新日期:2013-01-01 00:00:00
abstract::Nanotechnology is revolutionizing the development of different branches of science. The investigation of nanomaterials in the battle against cancer is not an exception. The main goal of this contribution is to bring an overview about the types of organic and inorganic nanomaterials that are under investigation for its...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140118213316
更新日期:2014-03-01 00:00:00