Abstract：
:Originally discovered as an anti-fungal agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a promising anti-cancer drug. In complex with its cellular receptor, the FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of the mammalian target of rapamycin (mTOR). By mediating amino acid sufficiency, mTOR governs signaling to translational regulation and other cellular functions by converging with the phosphatidylinositol 3-kinase (PI3K) pathway on downstream effectors. Whether mTOR receives mitogenic signals in addition to nutrient-sensing has been an unresolved issue, and the mechanism of action of rapamycin remained unknown. Our recent findings have revealed a novel link between mitogenic signals and mTOR via the lipid second messenger phosphatidic acid (PA), and suggested a role for mTOR in the integration of nutrient and mitogen signals. A molecular mechanism for rapamycin inhibition of mTOR signaling is proposed, in which a putative interaction between PA and mTOR is abolished by rapamycin binding. Collective evidence further implicates the regulation of the rapamycin-sensitive signaling circuitry by phospholipase D, and potentially by other upstream regulators such as the conventional protein kinase C, the Rho and ARF families of small G proteins, and calcium ions. As the mTOR pathway has been demonstrated to be an important anti-cancer target, the identification of new components and novel regulatory modes in mTOR signaling will facilitate the future development of diagnostic and therapeutic strategies.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Chen J,Fang Ydoi
10.1016/s0006-2952(02)01263-7subject
Has Abstractpub_date
2002-10-01 00:00:00pages
1071-7issue
7eissn
0006-2952issn
1873-2968pii
S0006295202012637journal_volume
64pub_type
杂志文章,评审abstract：:We have shown previously that (R)-5-fluoro-5,6-dihydrouracil (FUraH(2)) attenuates the antitumor activity of 5-fluorouracil (FUra) in rats bearing advanced colorectal carcinoma. Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decre...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00408-6
更新日期：2000-04-15 00:00:00
abstract：:The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90045-7
更新日期：1991-07-25 00:00:00
abstract：:The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor responsible for the recognition of potentially toxic endo- and exogenous compounds whose elimination from the body is accelerated by the CAR-mediated inducible expression of metabolizing enzymes and transporters. Despite the importance of CAR, few...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.08.014
更新日期：2008-11-15 00:00:00
abstract：:Hyperactivated macrophages play a key role in the initiation and perpetuation of mucosal inflammation in Crohn's disease (CD). Increasing evidence suggests that the basic helix-loop-helix (bHLH) repressor Twist1 can suppress activation of nuclear factor-κB (NF-κB) and the subsequent production of TNF-α, which are both...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.07.020
更新日期：2018-09-01 00:00:00
abstract：:The formation of triacylglycerols containing fenoprofen was studied in rat isolated adipocytes and hepatocytes incubated with [3H]glycerol and R or S fenoprofen. In both hepatocytes and adipocytes there was a high-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen which was stereospe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90537-0
更新日期：1988-05-15 00:00:00
abstract：:The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosp...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90473-v
更新日期：1992-10-20 00:00:00
abstract：:Several growth factor receptors undergo shedding from the cell surface as a result of limited proteolysis via mechanisms that are at present poorly understood. By Western blotting of the conditioned media and cell lysates of several cell lines expressing the hepatocyte growth factor receptor, we found that suramin, a ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00219-p
更新日期：1995-09-28 00:00:00
abstract：:We have investigated the redox behavior of a series of structurally related flavonoids employing cyclic voltammetry under physiological conditions. The flavonoids that auto-oxidized and produced oxygen radicals had oxidation potentials (E 1/2) significantly lower [-30 to +60 mV vs (SCE)] than those that did not underg...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90253-5
更新日期：1988-07-01 00:00:00
abstract：:A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-dip...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.10.015
更新日期：2012-01-15 00:00:00
abstract：:Cancer metastasis is a major cause for cancer-related death and inhibiting cancer metastasis is an alternative way to treat cancer. Several lines of reported evidence suggest that NADPH oxidase 4 (NOX4) is a potential target for intervention of cancer metastasis, as the reactive oxygen species (ROS) generated by this ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.05.011
更新日期：2013-07-15 00:00:00
abstract：:Imaging the pharmacodynamics of anti-cancer drugs may allow early assessment of anti-cancer effects. Increases in 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake early after thymidylate synthase inhibition (TS) inhibition, the so-called flare response, is considered to be largely due to an increase in binding s...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.004
更新日期：2010-11-15 00:00:00
abstract：:We have performed a systematic study of the interaction of 36 di- and tri-phenylethylene derivatives (DPEs and TPEs) with protein kinase C (PKC). The results were submitted to a multivariate analysis in order to identify the structural features that might be implicated in interference with the activity of three PKC su...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90448-e
更新日期：1991-09-12 00:00:00
abstract：:A newly-synthesized derivative of prazosin, prazosinamine hydrochloride, was examined for its ability to antagonize the interaction of the alpha 1-adrenergic agonist phenylephrine with liver cells. Using a Ca2--selective electrode to measure changes in perfusate Ca2+ concentration, prazosinamine was found to be as eff...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90040-2
更新日期：1987-05-15 00:00:00
abstract：:A comparative study of the N-B transition and the drug binding properties of human serum albumin samples from various sources has been carried out with the help of circular dichroism and equilibrium dialysis. It was found that when warfarin was used as a marker the midpoint pH and the cooperative nature of the N-B tra...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90293-3
更新日期：1982-12-01 00:00:00
abstract：:Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regula...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90385-1
更新日期：1988-10-01 00:00:00
abstract：:Son of Sevenless (SOS) was discovered in Drosophila melanogaster. Essential for normal eye development in Drosophila, SOS has two human homologues, SOS1 and SOS2. The SOS1 gene encodes the Son of Sevenless 1 protein, a Ras and Rac guanine nucleotide exchange factor. This protein is composed of several important domain...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2011.07.072
更新日期：2011-11-01 00:00:00
abstract：:Cisplatin is a potent chemotherapeutic drug widely used for the treatment of human cancer. However, its efficacy against hepatocellular carcinoma (HCC) is poor for reasons that remain unclear. We show here that prothymosin-alpha (PTMA) is overexpressed in HCC cell lines. Silencing PTMA using short-hairpin RNA sensitiz...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.10.003
更新日期：2016-12-15 00:00:00
abstract：:Oral administration of tobacco to rats for 21 days caused remarkable stimulation of the metabolism of phenacetin, aniline and benzo[a]pyrene, a carcinogen, by hepatic microsomal mixed function oxidases (MFO). Such treatment for 6 days resulted in a small increase in the activities of phenacetin O-dealkylase and aromat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90386-0
更新日期：1982-04-15 00:00:00
abstract：:Cardiorenal syndrome type-3 (CRS-3) is characterized by acute cardiac injury induced by acute kidney injury. Here, we investigated the causes of CRS-3 by analyzing cardiac function after renal ischemia-reperfusion injury (IRI) using echocardiography and evaluation of pro-inflammatory markers, calcium balance, mitochon...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113832
更新日期：2020-04-01 00:00:00
abstract：:N-[5-[N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2-thenoyl]-L-glutamic acid (ZD1694) is a folate-based thymidylate synthase (TS; EC 2.1.1.45) inhibitor. Metabolism to higher chain length polyglutamates is essential for its optimal cytotoxic effect. A ZD1694-resistant (300-fold) human ileocecal...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00135-m
更新日期：1995-07-31 00:00:00
abstract：:Naproxen, a non-steroidal anti-inflammatory drug, is known to be highly effective and relatively safe, but some side-effects in the liver have been reported. In the present study, the effect of naproxen metabolism on rat liver microsomes was studied by determining lipid peroxidation in terms of thiobarbituric acid rea...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90315-n
更新日期：1993-04-22 00:00:00
abstract：:Enhanced DNA repair activity is important for the development of cellular resistance to alkylating agents. Here, we quantitated the kinetics of DNA excision repairs initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells. CEM cells that had been established resistant to BCNU (CEM-R) w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00412-x
更新日期：2003-09-15 00:00:00
abstract：:Sulfation of tyrosyl residue(s) has been found to be a post-translational modification that precedes the secretion of many biologically active proteins or peptides. In the present paper, we report on the characterization of human liver tyrosylprotein sulfotransferase (TPST), the enzyme responsible for sulfation of tyr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90566-4
更新日期：1990-08-01 00:00:00
abstract：:Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90529-4
更新日期：1983-02-01 00:00:00
abstract：:The Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 (LY2), has been previously reported to inhibit nuclear factor κB (NFκB) activity, in a PI3K-independent mechanism. The goals of the current research were to determine the specificity of LY2 regarding NFκB subunits, and to identify relevant modulation of cyto...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.09.025
更新日期：2012-01-01 00:00:00
abstract：:This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads. Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01485-5
更新日期：2003-02-01 00:00:00
abstract：:Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in he...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90037-5
更新日期：1982-04-01 00:00:00
abstract：:Rat hepatocytes cultured in a sandwich configuration form functional canalicular networks. The influence of extracellular matrix configuration, medium composition, and confluency on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured (SC) rat hepatocytes was examined. Primary rat hepatocytes we...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.02.004
更新日期：2006-05-14 00:00:00
abstract：:Using a continuous perfusion system, synaptosomes prepared from rat brain released [3H]norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10(-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10(-5) M), a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90460-7
更新日期：1989-07-15 00:00:00
abstract：:Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been sy...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90020-5
更新日期：1994-01-20 00:00:00
