Abstract：
:JFCR39 is an informatic anticancer drug discovery system that utilizes a panel of 39 human cancer cells coupled with a drug-activity database. This system not only provides disease-oriented information but can also predict the mechanism of action of a given antitumor agent. Development of a phosphatidylinositol 3-kinase (PI3K) inhibitor as an anticancer drug candidate has attracted a great deal of attention from both academia and industry because PI3K is known to be closely involved in carcinogenesis. ZSTK474 was identified as a PI3K inhibitor using JFCR39 system in combination with COMPARE analysis program. These findings were based on the similar fingerprint (growth inhibition profiles for JFCR39 human cancer cell line panel) with that of a classical PI3K inhibitor LY294002. Biochemical experiments confirmed ZSTK474 to be a potent pan-class I PI3K inhibitor, with high selectivity over other classes of PI3K and protein kinases. We previously reported the in vitro and in vivo antitumor efficacy of ZSTK474, together with the G(0)/G(1) arrest and antiangiogenic activity. Here, we review the JFCR39 system and summarize recent studies on PI3K biology and the development of PI3K inhibitors before discussing ZSTK474 in some detail.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Kong DX,Yamori Tdoi
10.1038/aps.2010.150subject
Has Abstractpub_date
2010-09-01 00:00:00pages
1189-97issue
9eissn
1671-4083issn
1745-7254pii
aps2010150journal_volume
31pub_type
杂志文章,评审abstract：AIM:To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS:Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of cult...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-07-01 00:00:00
abstract：AIM:Toxicity of retinol (vitamin A) has been previously associated with apoptosis and/or cell malignant transformation. Thus, we investigated the pathways involved in the induction of proliferation, deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats. METHODS:Sertoli cells were i...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.202
更新日期：2012-04-01 00:00:00
abstract：AIM:The conventional method for analyzing 24-h ambulatory blood pressure monitoring (24-h ABPM) is insufficient to deal with the large amount of data collected. The aim of this study was to develop a novel cyclic fluctuation model for 24-h ABPM in Chinese patients with mild to moderate hypertension. METHODS:The data w...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：10.1038/aps.2013.45
更新日期：2013-08-01 00:00:00
abstract：AIM:To investigate the effect of chymase on the mucin secretion from human bronchial epithelial cells. METHODS:Primarily-cultured human bronchial epithelial (PCHBE) cells and normal human bronchial epithelial (NHBE) cells were cultured with chymase or other stimulus in a mixture of bronchial epithelial growth medium (...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-06-01 00:00:00
abstract：:Innovative teaching methodologies in different parts of the world are being practiced since last 3 decades. The aim of this review is to report the transition from traditional to innovative self learning process in Ziauddin Medical University, a new medical institute of Pakistan. Various problems encountered have been...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-09-01 00:00:00
abstract：:A variety of Ca2+ signals, in the form of intercellular pulses and waves, have been reported to be associated with the various sequential stages of somitogenesis: from convergent extension and the formation of the paraxial mesoderm; during the patterning of the paraxial mesoderm to establish segmental units; throughou...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2006.00401.x
更新日期：2006-07-01 00:00:00
abstract：AIM:To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS:One hundred and twenty-six renal transplant patients were recruited. Bl...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：10.1038/aps.2012.136
更新日期：2012-12-01 00:00:00
abstract：AIM:To evaluate single-dose and multiple-dose pharmacokinetics of cytotoxic T-lymphocyte-associated antigen 4 fusion protein (CTLA4Ig) in healthy volunteers and patients with rheumatoid arthritis (RA). METHODS:The clinical trials included two phase I open studies: study 1 was an open-label dose-escalation study in 27 ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.13
更新日期：2009-03-01 00:00:00
abstract：AIM:To investigate the effect of edaravone (MCI-186), a free radical scavenger, against ischemia/reperfusion (I/R) injury in the rat retina. METHODS:Retinal ischemia was induced in male Sprague-Dawley rats by elevating intraocular pressure to 110 mmHg for 60 min. The rats were intraperitoneally injected with edaravone...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00822.x
更新日期：2008-07-01 00:00:00
abstract：AIM:To search for novel effective P-glycoprotein (P-gp) reversal agents in the blood-brain barrier (BBB). METHODS:Using rhodamine123 (Rh123) to examine the functional activity of P-gp in cultured bovine brain capillary endothelial cells (BCEC) and screen various principles on P-gp modulation in BBB. RESULTS:All of te...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：:Single-target drugs have not achieved satisfactory therapeutic effects for complex diseases involving multiple factors. Instead, innovations in recent drug research and development have revealed the emergence of compound drugs, such as cocktail therapies and "polypills", as the frontier in new drug development. A trad...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2015.8
更新日期：2015-06-01 00:00:00
abstract：:Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A140...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0198-0
更新日期：2019-07-01 00:00:00
abstract：AIM:To study the changes of phospholipase D (PLD) activity of actively sensitized rat peritoneal mast cells (RPMC) in degranulation. METHODS:Degranulation of RPMC was determined by measurement of beta-hexosaminidase release. PLD activity assay was carried out by measurement of PLD product, choline, with chemiluminesce...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-01-01 00:00:00
abstract：AIM:To study the inhibitory effect of general gambogic acids (GGA) on transplantation tumor SMMC-7721 in experimental animal model and SMMC-7721 cells in vitro. METHODS:Anti-tumor activity of GGA in the experimental transplantation tumor SMMC-7721 was evaluated by relative tumor growth ratio. Cell morphology was obser...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-06-01 00:00:00
abstract：AIM:To explore correlation of T helper 1 (Th1) and Th2 cytokine between the cortical layer and pulmonary airway in ovalbumin-induced rat asthma model. METHODS:Aerosol antigen-induced changes of inflammation in bronchoalveolar lavage fluids (BALF) and pulmonary histologic section in sensitized rats were investigated. C...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：AIM:To study the alterations of myocardial taurine transport function, taurine transporter (TAUT), and cysteine sulfinate decarboxylase (CSD) mRNA as well as effect of exogenous taurine in rats with isoproterenol (ISO)-induced cardiomegaly. METHODS:[3H]-Taurine uptake and release on myocardium were determined. Binding...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：AIM:To investigate the effects of resveratrol on interleukin-1beta (IL-1beta) induced catabolism in bone marrow mesenchymal stem cell (MSC) derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS). METHODS:The chondrogenesis of alginate-encapsulated MSCs was evaluated by toluidine blue staining, RT-PCR, and i...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00880.x
更新日期：2008-11-01 00:00:00
abstract：AIM:To study the role of calcitonin gene-related peptide (CGRP) in nitric oxide (NO)-mediated myocardial delayed preconditioning induced by heat stress. METHODS:The isolated rat heart was perfused in a Langendorff model. Hearts for all groups were subjected to 4 h hypothermia (4 degrees C) and 40 min reperfusion (37 d...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：AIM:To test the ability of huperzine B (HupB) to alleviate injury from oxygen-glucose deprivation (OGD) in the rat pheochromocytoma line PC12 cells. METHODS:After OGD for 3 h and reoxygenation for 24 h, neuronal morphology was observed by phase-contrast microscopy; cell survival was quantified by the reduction of MTT;...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：AIM:Our previous study indicated that there are two types of Ca2+ release events seen in intact mouse bladder tissue. In this study our aim is to investigate the mechanism that underlies the phenomena of Ca2+ release in smooth muscle. METHODS:Single cells were isolated and tissue segments were prepared by cutting the ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00389.x
更新日期：2006-07-01 00:00:00
abstract：AIM:High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play pivotal roles in vascular inflammation and atherosclerosis. The aim of this study was to determine whether the HMGB1-RAGE axis was involved in the actions of simvastatin on vascular inflammation and atheroscler...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.8
更新日期：2013-06-01 00:00:00
abstract：AIM:To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. METHODS:The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei w...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.156
更新日期：2013-02-01 00:00:00
abstract：:As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capaci...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/s41401-020-0415-5
更新日期：2020-07-01 00:00:00
abstract：:Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in β-cells. Overexpression of txnip not only induces β-cell apoptosis but also reduces insulin production. Thus, t...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.15
更新日期：2017-07-01 00:00:00
abstract：AIM:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat, and their association with obesity-triggered increase in blood pressure. METHODS:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats. Control rats were fed wi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00810.x
更新日期：2008-10-01 00:00:00
abstract：AIM:G protein-coupled inwardly rectifying potassium channels (GIRK) are important for neuronal signaling and membrane excitability. In the present study, we intend to find whether GIRK channels express functionally in adult rat dorsal root ganglion (DRG) neurons. METHODS:We used RT-PCR to detect mRNA for 4 subunits of...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00478.x
更新日期：2007-02-01 00:00:00
abstract：AIM:To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (I(Ca-L)) in guinea pig ventricular myocytes. METHODS:Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, I(Ca-L) were recorded by whole-c...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-02-01 00:00:00
abstract：AIM:To investigate the effects of 3-n-butylphthalide (NBP) on apoptosis induced by transient focal cerebral ischemia in rats, compare the action potency of s-(-)-, r-(+)- and (+/-)-NBP, and clarify the enantiomer that played a main role. METHODS:DNA fragmentation was detected by the terminal deoxynucleotidyl transfera...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-08-01 00:00:00
abstract：AIM:To investigate the effect of epigallocatechin gallate (EGCG) on angiotensin II (Ang II)-induced stress fiber formation and hyperpermeability in endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVECs) were treated with Ang II in the absence or presence of EGCG or mitogen-activated protein kinases...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.75
更新日期：2010-10-01 00:00:00
abstract：:KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gli...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：10.1038/aps.2016.103
更新日期：2017-01-01 00:00:00
