Abstract：
:The effects of two new phthalazinone derivatives, azelastine (AZ) and flezelastine (FZ), on the reversal of resistance to doxorubicin (dox) were studied using two variants of the rat C6 glioblastoma cell line, selected with dox (C6 0.5) or with vincristine (C6 1V). Both lines presented a multidrug-resistant phenotype which was, in the case of C6 0.5 cells, likely to be accompanied by an additional mechanism leading to intracellular tolerance of the drug. Both AZ and FZ reversed dox resistance in a concentration-dependent manner, and FZ was shown to be at least three times more potent than AZ. FZ was able, at a relatively high concentration (30 microM), to completely restore dox sensitivity in both cell lines. Both drugs were able to virtually restore dox accumulation to the level reached in sensitive cells, and, interestingly, this complete restoration occurred at lower concentrations of modulator than required for complete reversal of resistance. FZ was able to reverse dox intracellular tolerance of C6 0.5 cells and to restore dox accumulation at the IC50 to the level observed in sensitive cells. AZ and FZ both inhibited azidopine binding to membrane preparations of C6 0.5 and C6 1V cells, although FZ was more potent. Both drugs more successfully inhibited azidopine binding to membranes prepared from C6 1V cells (which express the mdr1b gene product) than to membranes from C6 0.5 cells (which express the mdr1a gene product). In view of its potent activity on MDR, further preclinical evaluation of FZ is warranted.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hu YP,Robert Jdoi
10.1016/0006-2952(95)00130-rsubject
Has Abstractpub_date
1995-07-17 00:00:00pages
169-75issue
2eissn
0006-2952issn
1873-2968pii
000629529500130Rjournal_volume
50pub_type
杂志文章abstract：:A method for the isolation of an intact, non-covalent complex formed by the interaction of aldose reductase, NADP(H) nucleotide, and inhibitor has been developed to aid in the discovery and development of novel aldose reductase inhibitors. In the complexes isolated, both the carboxylic acid-containing inhibitor tolres...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00332-9
更新日期：2000-02-15 00:00:00
abstract：:Human flavin-dependent monooxygenase (FMO) isoforms 1 and 3 were expressed by retroviral gene transfer in mouse C3H/10T1/2 cells. FMO function was determined by the sulfoxidation of p-tolylmethylsulfide (TMS). Enzyme activity ranged from 4 to 30 nmol p-tolylmethylsulfoxide (TMSO)/30 min/mg cell protein for FMO 3 clone...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00978-4
更新日期：2002-06-01 00:00:00
abstract：:Human red blood cells and male Sprague-Dawley rats were treated in vitro and in vivo, respectively, with phenylhydrazine in order to determine whether the release of volatile hydrocarbons can serve as a suitable index for phenylhydrazine-induced red blood cell peroxidation. Lipid peroxidation following phenylhydrazine...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90338-1
更新日期：1984-06-01 00:00:00
abstract：:Nuclear factor-kappaB (NFKB) is a transcription factor with a pivotal role in inducing genes involved in physiological processes as well as in the response to injury and infection. A model has been proposed whereby the diverse agents that activate NFkappaB do so by increasing oxidative stress within the cell. Activati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(99)00296-8
更新日期：2000-01-01 00:00:00
abstract：:Site-specific DNA cleavage in the presence of Cu(II) complexes of podophyllotoxin derivatives was investigated with a modified Sanger sequencing method. Cu(II) complexes of 4'-demethylepipodophyllotoxin (DEPD) and syringic acid (SA) cleaved M13mp18 single-strand DNA site-specifically at both cytosine (C) and guanine (...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90324-7
更新日期：1994-05-18 00:00:00
abstract：:Ellipticine is a potent antineoplastic agent whose mechanism of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Recently, we found that ellipticine also forms covalent DNA adducts and that the formation of the major adduct is dependent on the activation of ellipticin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01072-9
更新日期：2002-07-15 00:00:00
abstract：:In vitro covalent binding of a chemically reactive metabolite of propranolol to microsomal macromolecules, which is presumed to cause inhibition of its own metabolism in rats, was diminished in liver microsomes from rats pretreated with propranolol. Covalent binding was suppressed by the addition of an antibody agains...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90587-8
更新日期：1994-11-16 00:00:00
abstract：:We investigated the mechanism of phorbol 12-myristate 13-acetate (PMA)-induced migration of glioblastoma cells focusing on the p38 mitogen-activated protein kinase (MAPK)/heat shock protein 27 (Hsp27) pathway. PMA-induced cell migration and activation of p38MAPK in A172 glioblastoma cells. PMA-induced formation of lam...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.06.018
更新日期：2007-09-01 00:00:00
abstract：:Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00306-3
更新日期：2000-06-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.02.010
更新日期：2005-05-01 00:00:00
abstract：:gamma-Aminobutyric acid (GABA) uptake was studied in bovine chromaffin cells maintained in primary culture. Uptake was found to be dependent on Na+, but not on K+ and Ca2+ ions; it was found that 2 Na+ ions were necessary for each molecule of GABA transported. 2,4-Dinitrophenol, ouabain and vanadate inhibited GABA upt...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90459-0
更新日期：1989-07-15 00:00:00
abstract：:Glimepiride and glibenclamide act apparently in a closely comparable manner upon both insulin and glucagon release. Except for the decreased efficiency of D-glucose in suppressing glucagon release after a prior exposure of the pancreas to the hypoglycemic sulfonylureas, no evidence was obtained to suggest that a posit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90435-8
更新日期：1991-09-27 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00148-2
更新日期：1997-07-01 00:00:00
abstract：:There is a strong association between tobacco smoking and the consumption of alcoholic beverages. When compared to the effects of either drug on its own, the combined use may lead to worsened outcomes, such as less successful quitting attempts and increased likelihood of developing mood disorders. Co-consumption most ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2017.06.113
更新日期：2017-11-15 00:00:00
abstract：:We have demonstrated earlier that a secreted fibroblast growth factor-binding protein (FGF-BP) can enhance angiogenesis and promote tumor growth in vivo. Furthermore, we found that FGF-BP expression in squamous cell carcinoma (SCC) is reduced by concentrations of retinoids that are effective in the treatment of SCC an...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00507-4
更新日期：2000-12-01 00:00:00
abstract：:The well-known analgesic and antipyretic drug N-acetyl-p-aminophenol (acetaminophen; APAP) has been previously reported to affect MDR1 expression in rat liver. In this study, we have investigated the effect of subtoxic doses of APAP on MDR1 expression and activity in rat intestine and human intestinal cells. Administr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.10.006
更新日期：2011-01-15 00:00:00
abstract：:Although clofibrate has been shown to inhibit platelet aggregation that is caused by thrombin, ADP and epinephrine, by blocking the release of arachidonic acid from platelet phospholipids [8], here we have demonstrated that clofibrate enhanced platelet aggregation by arachidonic acid and PLC and reversed the effects o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90434-8
更新日期：1982-06-01 00:00:00
abstract：:Cinnamaldehyde is a natural product from spices that inhibits cell separation in Bacillus cereus. Cell division is regulated by FtsZ, a prokaryotic homolog of tubulin. FtsZ assembles into the Z-ring at the site of cell division. Here, we report the effect of cinnamaldehyde on FtsZ and hence on the cell division appara...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.06.029
更新日期：2007-09-15 00:00:00
abstract：:Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucid...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.03.006
更新日期：2008-06-01 00:00:00
abstract：:Resistance to anti-cancer chemotherapies often leads to regional failure, and can be caused by biochemical and/or physiological mechanisms. Biochemical mechanisms include the overexpression of resistance-conferring proteins. In contrast, physiological resistance involves the tumor microenvironment, and can be caused b...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00467-2
更新日期：2003-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90300-x
更新日期：1994-05-18 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90505-9
更新日期：1988-03-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90365-4
更新日期：1984-01-01 00:00:00
abstract：:Glycerol enhances pulmonary tumorigenesis in mice treated with 4-nitroquinoline 1-oxide (4NQO). The present study shows that active oxygen formation by glycerol may be responsible for this enhanced tumorigenesis. Male ddY mice were treated with 4NQO and given a 5% glycerol solution instead of drinking water for up to ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90156-d
更新日期：1992-06-23 00:00:00
abstract：:Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane elect...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90684-w
更新日期：1991-06-21 00:00:00
abstract：:The kinetics of methotrexate inhibition of dihydrofolate reductase from Neisseria gonorrhoeae have been investigated. Methotrexate was shown to be a tight-binding inhibitor (Kt = 13 pM) competitive with dihydrofolate. However, "stoichiometric" or "pseudoirreversible" inhibition could not be demonstrated. Progress curv...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90579-3
更新日期：1984-07-01 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：:N-[(1,5,9)-trimethyldecyl]-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol (8-azadecalin 1), a high-energy intermediate analogue for the 2,3-oxidosqualene-lanosterol cyclase, was found to be a powerful (IC50 approximately 0.1 microM) inhibitor of cholesterol biosynthesis in human hepatoma HepG2 cells. In analogy with ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90222-4
更新日期：1994-07-05 00:00:00
abstract：:Duration of gene silencing due to the short-term silencing effects induced by exogenous siRNA have limited the therapeutic applications of RNAi and the development of RNAi-based therapeutics. We here generated Eg5 shRNA-expressing plasmids using the inverted terminal repeats (ITRs) sequences to produce Eg5 hairpin RNA...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.05.021
更新日期：2019-08-01 00:00:00
abstract：:We investigated the role played by monoclonal antibody defined classes of cytochrome P-450 in the metabolism of antipyrine, aminopyrine and theophylline. Two enzyme inhibitory monoclonal antibodies (MAb 1-7-1 and MAb 2-66-3) raised to two forms of cytochrome P-450 were used. Microsomes were prepared from the livers of...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90604-6
更新日期：1987-07-15 00:00:00
