Abstract:
:For many years the spotlight in drug discovery has been on a relatively small number of validated therapeutic target classes, such as G-protein coupled receptors and enzymes such as protein kinases, with well characterized enzymatic and cellular activities. However, with recent progress in genomics and proteomics, protein-protein interactions (PPIs) provide new way of finding novel bioactive molecules acting on their interfaces. This review addresses the current case studies and state of the art in the development of small chemical modulators controlling interactions of proteins that have pathological implications in various human diseases and in particular in cancer. The attention is focused on Bcl-2 family protein modulators ranging from natural products to synthetic ones with particular interest in foldamers as BH3 alpha helix mimetics.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
De Giorgi M,Voisin-Chiret AS,Rault Sdoi
10.2174/0929867311320240003subject
Has Abstractpub_date
2013-01-01 00:00:00pages
2964-78issue
24eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20130531-1journal_volume
20pub_type
杂志文章,评审abstract::Xanthones (dibenzo-γ-pyrones) constitutes an important class of oxygenated heterocycles and occur as secondary metabolites in plants and microorganisms. They are known for various biological activities such as antioxidant, monoamine oxidase inhibitor, antihypertensive, hepatoprotective, antithrombotic, antifungal and ...
journal_title:Current medicinal chemistry
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doi:10.2174/09298673113209990144
更新日期:2013-01-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and there...
journal_title:Current medicinal chemistry
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abstract::Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 family, is reported to exhibit a plethora of pleiotropic effects in the heart such as cytoprotective, pro-proliferative and pro-fibrotic ones. An extensive research has been devoted on proliferative and profibrotic effects of CT-1 on the heart. Thus the presen...
journal_title:Current medicinal chemistry
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doi:10.2174/092986713804806702
更新日期:2013-01-01 00:00:00
abstract::Patients with homozygous familial hypercholesterolemia (HoFH) represent the most severe patients within the spectrum of dyslipidemias. Untreated Low-Density Lipoprotein Cholesterol (LDL-C) levels in these patients are usually in the range 500 to 1200 mg/dL. Moreover, these patients exhibit a scarce responsiveness or e...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803341485
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Cholesterol efflux as a key event in reverse cholesterol transport (RCT) is considered now as both diagnostic tool and a promising target for the treatment of atherosclerosis. Radioactive in vitro cholesterol efflux assay (CEA) is the gold standard for determination of efflux at cellular level. Fluorescent t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160809093009
更新日期:2016-01-01 00:00:00
abstract::The rising emergence of antibiotic resistance urges the search for new strategies to defeat microorganisms that lead to persistent infections of the host. Tolerant to antibiotics, slowly replicating bacteria often cause latent and persistent infections that are the most challenging for pharmacological treatment. Persi...
journal_title:Current medicinal chemistry
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abstract::Histone deacetylase inhibitors have generated significant interest as anti-cancer agents due to their ability to cause growth arrest, terminal differentiation and/ or apoptosis in carcinoma cells. Abbott entered this area after the serendipitous discovery of the biaryl hydroxamate A-161906 in a TGF beta mimetic screen...
journal_title:Current medicinal chemistry
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abstract:BACKGROUND:In the last two decades, there have been significant technological advances in the early detection of brain tumors. However, no notable improvements have been observed in the treatment of Glioblastoma Multiforme (GBM), the most common brain neoplasm coupled with the worst prognosis. GBM is characterized by a...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867324666170303122241
更新日期:2017-01-01 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
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doi:10.2174/0929867326666190201142814
更新日期:2020-01-01 00:00:00
abstract::Normal somatic stem cells (SC) are naturally resistant to chemotherapeutic agents due to their expression of various membrane transporter molecules (such as MDR-1), detoxifying enzymes and DNA repair proteins. In addition, they also have a slow rate of cell turnover and therefore escape from chemotherapeutic agents th...
journal_title:Current medicinal chemistry
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更新日期:2009-01-01 00:00:00
abstract::Rapid innovations in nanomedicine have increased the likelihood that engineered nanomaterials will eventually come in contact with humans and the environment. The advent of nanotechnology has created strong interest in many fields such as biomedical sciences and engineering field. Central to any significant advances i...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710794183024
更新日期:2010-01-01 00:00:00
abstract::Hydroxypyridinones (HPs) are a family of N-heterocyclic metal chelators, which have been an attractive target in the development of a variety of new pharmaceutical drugs, due to their high metal chelating efficacy/specificity and easy derivatization to tune the desired biological properties. In fact, along the last de...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170330092304
更新日期:2018-01-01 00:00:00
abstract::Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell mi...
journal_title:Current medicinal chemistry
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doi:10.2174/092986706779026219
更新日期:2006-01-01 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:OBJECTIVES:Post-exercise cardiac troponin T (cTnT) release has been widely reported in adult athletes but limited data is available for adolescents. The aim of this study was to determine the incidence and magnitude of cTnT appearance in a large group of adolescent runners, and to determine any association between cTnT...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986711796642625
更新日期:2011-01-01 00:00:00
abstract::G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990168
更新日期:2013-01-01 00:00:00
abstract::The new drug class of dipeptidyl peptidase-4 (DPP4) inhibitors has been widely accepted in the daily management of type 2 diabetes since its strategic advantages with regard to body weight, risk of hypoglycaemia, and beta cell survival. We have previously evaluated the theoretical implications of DPP4 inhibition given...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986711797535290
更新日期:2011-01-01 00:00:00
abstract::Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval b...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666181016163110
更新日期:2020-01-01 00:00:00
abstract::The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The possibilities of treatment for oncological diseases are growing enormously in the last decades. Unfortunately, these developments have led to the onset of resistances with regards to the new treatments. This is particularly true if we face with the therapeutic field of Tyrosine Kinase Inhibitors (TKIs). ...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, f...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2006-01-01 00:00:00
abstract::From the discovery of Endothelial Progenitor Cells (EPC), these bone marrowderived precursors have been placed as crucial mediators of the endothelial repair. Accordingly, altered levels and function of EPC have been found in different scenarios of CV risk. Despite the fact that EPC exhibit important characteristics w...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract::Dose-limiting toxicity to healthy tissues is among the major hurdles in anticancer treatment along with intrinsic or acquired multi-drug resistance. Development of small molecule inhibitors (SMI) specific for antiapoptotic Bcl-2 proteins is a novel approach in a way that these antagonists are aimed to interfere with s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::Among the members of the 5'-nucleotidase family, there is only one membrane-bound ectosolic isoenzyme. This esterase prefers AMP as substrate but can hydrolyze a number of purine and pyrimidine phosphorylated compounds, indicating that no evolutive pressure to develop a more restricted specificity was exerted on this ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-01-01 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
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更新日期:2011-01-01 00:00:00
abstract::Protein C is a vitamin K-dependent anticoagulant serine protease zymogen in plasma which upon activation by the thrombin-thrombomodulin complex down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. In addition to its anticoagulant function, activated protein C (APC) also bi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791233706
更新日期:2010-01-01 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::Dipeptidyl peptidase 4 (DPP-4), a substrate-specific serine protease, has been validated as a promising drug target for the treatment of type 2 diabetes. DPP-4 inhibitors significantly lowered blood glucose levels in patients with type 2 diabetes without common body weight gain, hypoglycemia and gastrointestinal distu...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712802002491
更新日期:2012-01-01 00:00:00
abstract::Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707780090981
更新日期:2007-01-01 00:00:00
abstract::Frontotemporal Lobar Degeneration (FTLD) is characterized by behavioral changes, executive dysfunctions, and language impairment, sustained by different neuropathological patterns. The collective efforts of clinical, pathological and genetic studies have recently opened new insights into the underpinnings of pathologi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712799320637
更新日期:2012-01-01 00:00:00