Abstract：
:Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal' cells and a lack of tumour selective targeting, resulting in a therapeutic index which is modest at best. Consequently, the development of more tumour selective cancer treatments, with better discrimination between tumour and normal cells is unequivocally an important goal for cancer drug discovery. One such strategy is to exploit the tumour phenotype as a mechanism for tumour-selective delivery of potent therapeutics. An exciting approach in this area is to develop anticancer therapeutics as prodrugs, which are non-toxic until activated by enzymes localized specifically in the tumour. Enzymes suitable for tumour-activated prodrug development must have increased activity in the tumour relative to non-diseased tissue and an ability to activate the prodrug to its active form. One class of enzyme satisfying these criteria are the tumour endoproteases, particularly the serine- and metallo-proteases. These proteolytic enzymes are essential for tumour angiogenesis, invasion and metastasis, the major defining features of malignancy. This review describes the concept behind development of tumour-endoprotease activated prodrugs and discusses the various studies to date that have demonstrated the huge potential of this approach for improvement of cancer therapy.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Atkinson JM,Siller CS,Gill JHdoi
10.1038/sj.bjp.0707657subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1344-52issue
7eissn
0007-1188issn
1476-5381pii
0707657journal_volume
153pub_type
杂志文章,评审abstract：:1. [125I]-Tyr4-bombesin exhibited saturable binding to pancreatic acinar cells. 2. Preincubation of cells at 37 degrees C with 0.03 nM-1 microM-bombesin for 10 min followed by acid or neutral washes reduced subsequent binding of [125I]-Tyr4-bombesin in a concentration-dependent manner by up to 90%. 3. In cell suspensi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13187.x
更新日期：1994-08-01 00:00:00
abstract：:1. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14430.x
更新日期：1992-08-01 00:00:00
abstract：:1. Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2. In the extrameningeal arteries, transmural electrical stimulation produced a phasic contracti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb17207.x
更新日期：1995-11-01 00:00:00
abstract：:1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150-300 microm in diameter) arteries o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701610
更新日期：1998-01-01 00:00:00
abstract：:1. By use of the whole-cell configuration of the patch-clamp technique, membrane currents induced by cyclopiazonic acid (CPA; an inhibitor of the sarcoplasmic reticulum (SR) calcium-ATPase) were investigated in single smooth muscle cells freshly dispersed from the mouse anococcygeus. Voltage-dependent calcium currents...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15228.x
更新日期：1996-02-01 00:00:00
abstract：:Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)-like material on field stimulation. The release of SP-like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10254.x
更新日期：1986-07-01 00:00:00
abstract：:1. In order to determine whether activation of adenosine triphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimenta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12294.x
更新日期：1991-05-01 00:00:00
abstract：:1. The ability of PD 128907 to activate dopamine receptors in the ventral tegmental area, substantia nigra pars compacta, and striatum was investigated by use of in vitro electrophysiological recording and fast cyclic voltammetry. The affinity of a novel D2 selective antagonist L-741,626 for receptors activated by thi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb16063.x
更新日期：1996-12-01 00:00:00
abstract：:1. Depolarization of rat cerebral cortical slices, prelabelled with [3H]-histidine, in high potassium (40 mM KCl) medium stimulated the release of [3H]-histamine. The K+-evoked release of [3H]-histamine was attenuated by incubation in calcium-free medium and prevented by prior incubation of brain slices with the selec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11758.x
更新日期：1988-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pemphigus and pemphigoid diseases are characterized and caused predominantly by IgG autoantibodies targeting structural proteins of the skin. Their current treatment relies on general and prolonged immunosuppression that causes severe adverse events, including death. Hence, novel safe and more ef...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14986
更新日期：2020-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Ajmaline is a widely used antiarrhythmic drug. Its action on voltage-gated ion channels in skeletal muscle is not well documented and we have here elucidated its effects on Na(+) and K(+) channels. EXPERIMENTAL APPROACH:Sodium (I(Na)) and potassium (I(K)) currents in amphibian skeletal muscle fi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707194
更新日期：2007-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tanshinol borneol ester (DBZ) is a novel synthetic compound derived from Dantonic® , a botanical drug approved in 26 countries outside the United States for angina pectoris and currently undergoing FDA Phase III clinical trial. Here, we investigated the angiogenic effects of (S)-DBZ and (R)-DBZ i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14714
更新日期：2019-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01453.x
更新日期：2012-02-01 00:00:00
abstract：:1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/k...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08256.x
更新日期：1973-08-01 00:00:00
abstract：:1. Poly(2-vinylpyridine 1-oxide) counteracts the pathogenic effects normally produced when quartz is injected into or inhaled by animals and the cytotoxic effects when quartz is added to macrophage cultures. The protective action of this polymer has been attributed variously to the formation of an adsorbed layer on th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10347.x
更新日期：1970-01-01 00:00:00
abstract：:1 The actions of prostaglandin F2 alpha (PGF2 alpha) and noradrenaline on contraction and 45Ca exchange have been studied in rat mesenteric arteries. 2 PGF2 alpha and noradrenaline contracted rat isolated mesenteric artery preparations to about the same extent. The PGF2 alpha-stimulated contractions, unlike those prod...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08777.x
更新日期：1982-01-01 00:00:00
abstract：:1. The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Ta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12275.x
更新日期：1991-04-01 00:00:00
abstract：:To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]-taurine efflux from acutely isolated SON. Taurine release induced by hypotonic stimulus (25...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703492
更新日期：2000-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:There is growing evidence that inflammation plays a major role in the pathogenesis of neural damage caused by deposition of amyloid β (Aβ) in the brain. Nimodipine has received attention as a drug that might improve learning and reduce cognitive deficits in Alzheimer's disease, but the mechanism ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02112.x
更新日期：2012-12-01 00:00:00
abstract：LINKED ARTICLES:This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc. ...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/bph.14371
更新日期：2018-08-01 00:00:00
abstract：:1. The present study investigated the central effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the role of 5-hydroxytryptamine(3) (5-HT(3)) receptors in the core of the nucleus accumbens (NAc) on cocaine-induced behavioural changes in rats. 2. The 5-HT(3) receptor antagonist ondansetron (1 o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703687
更新日期：2000-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 n...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14068
更新日期：2018-06-01 00:00:00
abstract：:1. The effects of bretylium have been investigated on the content and sub-cellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve.2. Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09887.x
更新日期：1970-04-01 00:00:00
abstract：:1. The calcium sensitivity of force production of cardiac muscle fibres is altered by certain drugs. The sites of action of three such compounds (pimobendan, sulmazole, isomazole) within the myofibril have been investigated. Calmodulin antagonists, perhexilene and bepridil, which have been shown to alter the calcium d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14092.x
更新日期：1990-08-01 00:00:00
abstract：:The effects of local perivascular application of dopamine to rat pial arterioles. (20-40 micrometer i.d.) were examined in situ, at the microcirculatory level, by use of a high-resolution closed circuit television microscope recording system. Local application of very low, physiological doses (1 to 10 pg) of dopamine ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07900.x
更新日期：1980-08-01 00:00:00
abstract：:The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704768
更新日期：2002-06-01 00:00:00
abstract：:1. Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators part...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15081.x
更新日期：1995-11-01 00:00:00
abstract：:1. The present study characterizes and classifies alpha 1-adrenoceptor-mediated vasoconstriction in the isolated perfused kidney of rat using quantitative receptor pharmacology and compares the results to radioligand binding studies (made in cloned alpha 1-adrenoceptor subtypes, native alpha 1A-adrenoceptors in submax...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15875.x
更新日期：1995-05-01 00:00:00
abstract：UNLABELLED:Sarcoplasmic reticular (SR) Ca(2+) -ATPase (SERCA2a) is central to cardiac electrophysiological and mechanical function. It ensures full diastolic relaxation minimizing delayed after-potentials that would otherwise compromise membrane electrophysiological stability, and optimizes SR Ca(2+) refilling and syst...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1111/bph.12288
更新日期：2013-10-01 00:00:00
abstract：:1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704421
更新日期：2001-12-01 00:00:00
