Abstract:
:Stress or heat shock proteins (Hsps) Hsp90, Hsp70 and Hsp27 are chaperones that assist the proteins in their folding, stability, assembly into multi-protein complexes and transport across cellular membranes. The expression of some of them is highly induced in response to a wide variety of physiological and environmental insults. Hsps have a dual function depending on their intracellular or extracellular location. Intracellular Hsps have a protective function. They allow the cells to survive to lethal conditions. The cytoprotective functions of Hsps can largely explain by their anti-apoptotic properties. Hsp90, Hsp70 and Hsp27 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of Hsp27, Hsp70 and/or Hsp90 is frequently abnormally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of Hsps has become an interesting strategy in cancer therapy. In contrast to intracellular Hsps, extracellular located or membrane-bound Hsps mediate immunological functions. They can elicit an immune response modulated either by the adaptive or innate immune system. In cancer, most immunotherapeutical approaches based on extracellular Hsps exploit their carrier function for immunogenic peptides. This review will discuss this different and often paradoxical approaches in cancer therapy based on the dual role of Hsps, protective/tumorigenic versus immunogenic.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Didelot C,Lanneau D,Brunet M,Joly AL,De Thonel A,Chiosis G,Garrido Cdoi
10.2174/092986707782360079subject
Has Abstractpub_date
2007-01-01 00:00:00pages
2839-47issue
27eissn
0929-8673issn
1875-533Xjournal_volume
14pub_type
杂志文章,评审abstract::Pentacyclic triterpenoids including the oleanane, ursane and lupane groups are widely distributed in many medicinal plants, such as Glycyrrhiza species, Gymnema species, Centella asiatica, Camellia sinensis, Crataegus species and Olea europaea, which are commonly used in traditional medicine for the treatment of diabe...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation. Because the population in the West...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706776360987
更新日期:2006-01-01 00:00:00
abstract::Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. Nevertheless, their intake is frequently associated with gastrointestinal side effects, representing still an important medical and socio-economic problem. In recent years efforts focused on the development of highly select...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788682209
更新日期:2009-01-01 00:00:00
abstract::The existence of functional NT/dopamine interactions in the central nervous system has been extensively documented. Among others, a possible molecular mechanism underlying the NT-induced modulation of dopamine release is a direct antagonistic NTS(1)/D(2) receptor interaction. More recently, neurochemical experiments a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803414268
更新日期:2012-01-01 00:00:00
abstract::Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder. The mainstay of coeliac disease treatment is strict life...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782023343
更新日期:2007-01-01 00:00:00
abstract::APN is an important zinc dependent metallo-exopeptidase; it has been considered as a suitable target for anti-cancer drug design. In this review we focus on the most effective and the most promising inhibitors of aminopeptidase N. Their binding modes to the enzyme, the attempt to explain the origin of the inhibitory a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708786242840
更新日期:2008-01-01 00:00:00
abstract::The oxime formation reaction of therapeutical progestogen (levonorgestrel, levonorgestrel acetate, norethisterone), androgen (methyltestosterone, testosterone phenylpropionate) and anabolic (nortestosterone phenylpropionate) Delta(4)-3-ketosteroids has been investigated. The ketosteroid-hydroxylamine reaction was moni...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867013372238
更新日期:2001-09-01 00:00:00
abstract::Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782023659
更新日期:2007-01-01 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::Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first committed step of guanosine 5'-monophosphate (GMP) biosynthesis, and thus regulates the guanine nucleotide pool, which in turn governs proliferation. Human IMPDHs are validated targets for immunosuppressive, antiviral and anticancer drugs, but as yet m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795590129
更新日期:2011-01-01 00:00:00
abstract::The bi-aryl urea multi-kinase inhibitor Sorafenib (BAY 43-9006, Nexavar) was initially approved for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. Eleven years after its first description in PubMed, the therapeutic potential of Sorafenib has been evaluated in an increasing nu...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803341548
更新日期:2012-01-01 00:00:00
abstract::The serine protease thrombin is a key enzyme in the control of blood coagulation and displays numerous other effects on platelet, endothelial and smooth muscle cell function. The pre-eminence of thrombin in the coagulation cascade has made the enzyme a popular drug target in the search for more clinically acceptable a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1998-12-01 00:00:00
abstract::Cellular resistance to anthracyclines is a major limitation of their clinical use in the treatment of human tumors. Resistance to doxorubicin is described as a multifactorial phenomenon involving the overexpression of defense factors and alterations in drug-target interactions. Such changes do not account for all mani...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013373994
更新日期:2001-01-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140826114135
更新日期:2014-01-01 00:00:00
abstract::Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) belong to the protein family of neurotrophins. They both display profound neuromodulatory functions and are essentially involved in the survival and homeostatic maintenance of central and peripheral neurons during development and adulthood. Moreove...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707781745578
更新日期:2007-01-01 00:00:00
abstract::The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfur-containing congeners, and the isolation of clavulanic acid, a potent inhibitor of beta-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and ce...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043364883
更新日期:2004-07-01 00:00:00
abstract::Nowadays, the use of synthetic carriers as biochemical reagents and immunogens is entering a new phase. The multimeric nature of these constructs, the unambiguous composition and the ease, reliability and versatility of their production, make this type of carriers well-suited to various biotechnological and biochemica...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867054039062
更新日期:2005-01-01 00:00:00
abstract::With the recent market approval of Pitolisant (Wakix®), the interest in clinical application for novel multifunctional histamine H3 receptor antagonists has clearly increased. Several combinations of different H3R pharmacophores with pharmacophoric elements of other G-protein coupled receptors, transporters or enzymes...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666200806103144
更新日期:2020-08-05 00:00:00
abstract::Protein p53 is a key player in mitochondrial mediated apoptotic cell death and excess p53 activity has been implicated in many disease states such athrosclerosis, diabetes, osteoarthritis, Alzheimer's disease, Parkinson's disease, Huntington's disease, AIDS, P. falciparum and S. typhimurium infections. Thus, chemical ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788681976
更新日期:2009-01-01 00:00:00
abstract::Kinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact on human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180926154329
更新日期:2019-01-01 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::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::The maximum therapeutic potentials of pharmacologically active molecules are generally not attained due to their non specific delivery. Ligands associated with drug or delivery system through which it is delivered provide navigation and direction to the carrier system(s) so as to reach and release bioactive(s) at the ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707781368432
更新日期:2007-01-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidne...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170414162841
更新日期:2017-01-01 00:00:00
abstract::A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have incr...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457133
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as Protein Interaction Domains (PIDs). OBJECTIVE:This review concerns with PIDs rec...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190620101637
更新日期:2020-01-01 00:00:00
abstract::For more than 20 years there has been increasing interest in the development of novel therapies to raise levels of high-density lipoprotein cholesterol (HDL-C). However, well publicized failures of recent clinical trials of agents that raise HDL-C levels have stimulated considerable controversy with regard to the pote...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140414104130
更新日期:2014-01-01 00:00:00
abstract::Fluoxetine is an antidepressant drug, a potent and specific inhibitor of serotonin reuptake (SSRI). Evidence suggests that being compared with tricyclic antidepressants, fluoxetine may cause significantly fewer anticholinergic, antihistaminergic and cardiotoxic side effects in the treatment of major depressive disorde...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:Pregnancy specific β1-glycoproteins (PSGs) have long been recognized as trophoblast quality and embryo viability markers. However, biological roles of PSGs remain obscure, and structure/function relationships to other feto-placental proteins as well as implications for drug design have not been reviewed. Thi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666161123090554
更新日期:2017-01-01 00:00:00
abstract::In the last decade much attention has been paid to the development of metabolically non-reversible dimeric or hybrid compounds, which combine two structural units of one or two lead compounds of interest for the treatment of Alzheimer's disease. As a consequence of their capability to simultaneously interact with two ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706775527974
更新日期:2006-01-01 00:00:00