Abstract:
:Quinone based bioreductive drugs have, potentially, a very versatile use in cancer chemotherapy. They can be activated by DT-diaphorase and hence can be used to target tumour types rich in this (O2)-independent reductase enzyme. Small molecular modifications can substantially reduce specificity for DT-diaphorase and under these circumstances the quinones become much less toxic in air but retain their potent cytotoxic effects under hypoxic conditions. Our understanding of the reductive (bio) chemistry of indolequinones, in particular, has subsequently allowed us to develop a platform technology where almost any therapeutic entity can potentially be delivered, selectively, to hypoxic tumours. Antiangiogenic approaches are currently receiving a substantial amount of attention and this review brings their development into context in view of the hypoxia dependence for neovascularization. Lastly, the use of bioreductive drugs when combined with hypoxia-mediated gene therapy is described. Such an approach provides a unique dual level of specificity for targeting hypoxic tumours and potentially can provide substantial therapeutic benefit.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
McNally VA,Patterson AV,Williams KJ,Cowen RL,Stratford IJ,Jaffar Mdoi
10.2174/1381612023394548subject
Has Abstractpub_date
2002-01-01 00:00:00pages
1319-33issue
15eissn
1381-6128issn
1873-4286journal_volume
8pub_type
杂志文章,评审abstract::In the present review, associations between traditional vascular risk factors (VRFs) and carotid intimamedial thickness progression (C-IMTp) as well as the effects of therapies for VRFs control on C-IMTp were appraised to infer causality between each VRF and C-IMTp. Cohort studies indicate that smoking, binge drinking...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191213120339
更新日期:2020-01-01 00:00:00
abstract::Pyrimidine nucleotides, including UTP, UDP and UDP-glucose, are important signaling molecules which activate G protein-coupled membrane receptors of the P2Y family. Four distinct pyrimidine nucleotide-sensitive P2Y receptor subtypes have been cloned, P2Y(2), P2Y(4), P2Y(6) and P2Y(14). Pharmacological experiments indi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023392937
更新日期:2002-01-01 00:00:00
abstract::A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210790883499
更新日期:2010-01-01 00:00:00
abstract::Chronic smoking is associated with functional and structural vascular changes underlying inflammatory processes responsible for plaque formation and rupture. Cyclooxygenase (COX) is the key enzyme linking smoking action to inflammatory damages: it is responsible for the conversion of arachidonic acid to prostanoids, a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210792062902
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance. METHODS:We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161282001140113125143
更新日期:2014-01-01 00:00:00
abstract::First generation drug-eluting stents (DES) have significantly improved the treatment options for patients with symptomatic coronary artery disease by decreasing rates of acute vessel closure and restenosis after percutaneous coronary revascularization procedures. However, early enthusiasm was temperd by reports of lat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794454879
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Nuts have been an indispensable component of the human diet for hundreds because of their unique nutrient composition and are thought to play a beneficial part in the prevention of cardiovascular diseases. OBJECTIVE:To evaluate the extent, validity and presence of evidence for studies investigating the impa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612822666161010121356
更新日期:2017-01-01 00:00:00
abstract::Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). One of the key triggers of DNA single strand breakage in pathophysiological conditions is peroxynitrite, a reactive species produced from the reaction of nitric oxide and superoxid...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947579
更新日期:2006-01-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) includes liver diseases ranging from simple steatosis to progressive forms characterized by high rates of complications and mortality, namely fibrosis, cirrhosis and hepatocellular carcinoma. Identification of patients with simple steatosis who will evolve to a more severe liv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191122101021
更新日期:2020-01-01 00:00:00
abstract::No-reflow, i.e., the lack of distal myocardial perfusion to fully recover following recanalization of an acutely occluded coronary artery, is not only a mere consequence of ischemic injury, as substantial microvascular alterations may also develop subsequently, after initial restoration of perfusion. Since part of per...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990357
更新日期:2013-01-01 00:00:00
abstract::Histone deacetylases (HDACs), which act on acetylated histones and/or other non-histone protein substrates, represent validated epigenetic targets for the treatment of cancer and other human diseases. The inhibition of HDAC activity was shown to induce cell cycle arrest, differentiation, apoptosis as well as a decreas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141110164604
更新日期:2015-01-01 00:00:00
abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200824104856
更新日期:2020-08-23 00:00:00
abstract::Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Med...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200831151316
更新日期:2020-01-01 00:00:00
abstract::In recent years, our understanding of the molecular interaction of collagens with their cognate integrin receptors has remarkably improved. Structural elucidations of both the integrin and the collagenous triple helix have contributed to this achievement. The structures of an entire integrin ectodomain and of an A-dom...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381738
更新日期:2005-01-01 00:00:00
abstract::Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200730220230
更新日期:2020-01-01 00:00:00
abstract::The production of autoreactive antibodies from self-reactive B cells results in the formation of immune complexes that deposit in tissue and fix complement, contributing to the pathogenesis of rheumatoid arthritis (RA). Earlier mouse models emphasize the importance of autoreactive antibodies formed against "self" prot...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381936
更新日期:2005-01-01 00:00:00
abstract::Growth and metastasis of lung cancer requires a sequence of events, which alter the ability of neoplastic cells to adhere to themselves, to normal surrounding cells, or to the extracellular matrix. Interactions between cells are primarily mediated by four types of structures in the plasma membrane: gap junctions, tigh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785740162
更新日期:2008-01-01 00:00:00
abstract::Lipid markers are well established predictors of vascular disease. The most frequently measured lipid variables are total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. In this review we consider the predictive value of these variables and other more specialis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367409
更新日期:2005-01-01 00:00:00
abstract::Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This pap...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990600
更新日期:2014-01-01 00:00:00
abstract::The triggering receptor expressed on myeloid cells (TREM)-1 is a member of the Ig-like immunoregulatory receptor family and a major amplifier of innate immune responses. TREM- 1 has been implicated in the development and perpetuation of a number of inflammatory disorders, and soluble TREM-1 levels are a clinically val...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160826110539
更新日期:2016-01-01 00:00:00
abstract::Rotaviruses are an important cause of human morbidity and mortality, representing the primary pathogens responsible for acute dehydrating diarrhea in children under the age of 3. The infectious rotavirus particle is made up of three concentric layers of protein, and contains a genome consisting of eleven segments of d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382620
更新日期:2004-01-01 00:00:00
abstract::An important goal of biomedical research is to translate basic research findings into practical clinical implementation. Despite the advances in the technology used in drug discovery, the development of drugs for central nervous system diseases remains challenging. The failure rate for new drugs targeting important ce...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200224112534
更新日期:2020-01-01 00:00:00
abstract::With a 2030 projection of 23.6 million deaths per year the prevalence and severity of cardiovascular disease is at an astounding high. Thus, a definitive need for the identification of novel compounds with potential to prevent or treat the disease and associated states. Moreover, there is also an ever-increasing need ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200909125354
更新日期:2020-09-09 00:00:00
abstract::The beneficial effect of antihypertensive treatment on the risk of major vascular events is well established. Several trials comparing older and newer drugs in the treatment of primary hypertension suggested that it is the blood pressure achieved, rather than choice of the drug that determines most of the primary outc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207779313713
更新日期:2007-01-01 00:00:00
abstract::G-quadruplexes have found increasing potential in applications such as molecular therapeutics, diagnostics, and sensing. As a consequence, small molecules capable of selectively detecting G-quadruplexes have received significant attention in recent literature. Our review here addresses representative advances in the d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799958314
更新日期:2012-01-01 00:00:00
abstract::In recent years, nanosuspensions have been accepted as a valuable drug delivery system for poorly water-soluble drugs. Topdown and bottom-up technologies are the two main approaches for generating nanosuspensions. Several products manufactured by the top-down technologies have been successfully commercialized demonstr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990401
更新日期:2014-01-01 00:00:00
abstract::There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788957438
更新日期:2009-01-01 00:00:00
abstract::The organ shortage for kidney transplantation remains a challenging issue worldwide. Incompatibility between donor-recipient pairs, commonly occurring among transplant candidates who were sensitized from prior antigen exposure, serves as a significant barrier to kidney transplantation. In efforts to overcome this obst...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200521141749
更新日期:2020-01-01 00:00:00
abstract::The deregulated proteolysis is associated with various diseases in humans. Proteases are commonly regarded as the therapeutic targets. Almost one-third of all proteolytic enzymes in humans are serine proteases. This work provides a brief characteristic of the proteinaceous natural inhibitors, mostly of serine protease...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141027113923
更新日期:2015-01-01 00:00:00