Abstract:
:The new olivacine derivative S16020-2 (NSC-659687) is a DNA topoisomerase II inhibitor endowed with a remarkable antitumor activity against various experimental tumors. In vitro physicochemical properties of this compound, in particular its interaction with DNA and DNA topoisomerase II, were very similar to those of ellipticine derivatives, except for a strictly ATP-dependent mechanism of cleavable complex induction. From the Chinese hamster lung fibroblast cell line DC-3F, a subline resistant to S16020-2, named DC-3F/S16, was selected by adding stepwise increasing concentrations of the drug to the cell growth medium. Whereas DC-3F/9-OH-E cells, a DC-3F subline resistant to 9-hydroxy-ellipticine, are cross-resistant to S16020-2, DC-3F/S16 cells are only very weakly cross-resistant to ellipticine derivatives, indicating that, despite their structural similarity, these compounds may differ in their mechanisms of action. Uptake and efflux rates of S16020-2 were identical in the resistant and the sensitive cells. Topoisomerase IIalpha was expressed at the same level in both sensitive and resistant cells, whereas expression of the beta-enzyme was approximately 50% lower in the resistant cells. Sequencing of both alpha- and beta-isoform cDNAs revealed a point mutation that converts Arg(486) to a Gly in the alpha cDNA, whereas the beta cDNA was not modified. This amino acid substitution in a highly conserved sequence of the enzyme appears to be responsible for the resistance to S16020-2. Comparative analysis of the properties of the ellipticine and S16020-2-resistant cells suggests that S16020-2, which is a DNA intercalator, might also interact with this enzyme amino acid sequence through its side chain.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Le Mée S,Chaminade F,Delaporte C,Markovits J,Saucier JM,Jacquemin-Sablon Adoi
10.1124/mol.58.4.709keywords:
subject
Has Abstractpub_date
2000-10-01 00:00:00pages
709-18issue
4eissn
0026-895Xissn
1521-0111journal_volume
58pub_type
杂志文章abstract::The NO/cGMP signaling pathway plays a major role in the cardiovascular system, in which it is involved in the regulation of smooth muscle tone and inhibition of platelet aggregation. Under pathophysiological conditions such as endothelial dysfunction, coronary artery disease, and airway hyperreactivity, smooth muscle ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020909
更新日期:2006-06-01 00:00:00
abstract::The ability of four antidepressant drugs, imipramine, alaproclate, norzimelidine, and fluvoxamine, to inhibit serotonin transport into platelet plasma membrane vesicles was tested over a range of external Na+ concentrations. Imipramine affinity, as we previously reported [J. Biol. Chem. 258:6115-6119 (1983)] increases...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::In cervical cancer, the p53 and retinoblastoma (pRb) tumor suppressor pathways are disrupted by the human papilloma virus (HPV) E6 and E7 oncoproteins, because E6 targets p53 and E7 targets pRb for rapid proteasome-mediated degradation. We have investigated whether E6 suppression with small interfering RNA (siRNA) res...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.076539
更新日期:2012-05-01 00:00:00
abstract::Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upre...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.106005
更新日期:2016-11-01 00:00:00
abstract::Cytochrome P450 2C6 (CYP2C6) is a developmentally regulated, constitutively expressed form of rat liver microsomal cytochrome P450 that in the liver of adult male rats is induced to a limited extent by phenobarbital. The gene is not expressed at detectable levels in the lung, kidney, or brain. It is expressed and indu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Monoclonal antibodies specific for cytochromes P-450 induced by 3-methylcholanthrene (Mab 1-7-1) and phenobarbital (Mab 2-66-3) have been used in an unlabeled peroxidase-antiperoxidase immunohistochemical procedure to investigate the intralobular distribution and induction sites of the hemoproteins within the livers o...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Using [3H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-se...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Nicotine biotransformation affects the smoking habits of addicted individuals and therefore their health risk. Using an improved analytical method, we have discovered that the human UDP-glucuronosyltransferase (UGT) 2B10, a liver enzyme previously unknown to conjugate nicotine or exhibit considerable activity toward a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.037093
更新日期:2007-09-01 00:00:00
abstract::Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.089631
更新日期:2014-02-01 00:00:00
abstract::Nefiracetam (DM-9384) is a new pyrrolidone nootropic drug being developed for the treatment of Alzheimer's type and poststroke vascular-type dementia. Because the cholinergic system plays an important role in cognitive functions and Alzheimer's disease dementia, the present study was conducted to elucidate the mechani...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.4.674
更新日期:2001-04-01 00:00:00
abstract::The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.5.816
更新日期:1997-05-01 00:00:00
abstract::Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked ...
journal_title:Molecular pharmacology
pub_type: 杂志文章,收录出版
doi:10.1124/mol.110.067512
更新日期:2011-02-01 00:00:00
abstract::Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play an important role in the regulation of cell physiology in a wide variety of excitable and nonexcitable tissues. Filamin A is a conserved and ubiquitous actin-binding protein that forms perpendicular actin cross-links and contributes to changes in cell shap...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.038026
更新日期:2007-09-01 00:00:00
abstract::Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S)-6-((1-(4-chlorophenyl)eth...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.099747
更新日期:2015-11-01 00:00:00
abstract::The chemical reaction of 1,4-benzoquinone with glutathione results in the formation of adducts that exhibit increasing degrees of glutathione substitution. Purification of these adducts and analysis by 1H and 13C nuclear magnetic resonance spectroscopy revealed the products of the reaction to be 2-(glutathion-S-yl)hyd...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::To enable the detailed pharmacological characterization of five bombesin (BN) analogs with respect to the human gastrin-releasing peptide (GRP) receptor, we ectopically expressed the receptor in BALB/3T3 cells. In such cells (termed GR1 cells), GRP stimulated DNA synthesis and Ca2+ mobilization. Two of these analogs, ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 4...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::[This corrects the article on p. 21 in vol. 81, PMID: 21984254.]. ...
journal_title:Molecular pharmacology
pub_type: 已发布勘误
doi:10.1124/mol.115.075234err
更新日期:2016-01-01 00:00:00
abstract::Antibodies against synthetic peptides of the D2 dopamine receptor were used, in combination with photoaffinity labeling, to localize the region of ligand binding in the receptor. Specific antibodies to peptide sequences 221-234 and 259-272 and to the carboxyl-terminal peptide 402-415, all corresponding to cytoplasmic ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Specific toxic and biochemical responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human thymic epithelial (TE) cells in culture are mediated by the TCDD receptor protein. Characterization of the physicochemical properties of the TCDD receptor in cytosol fractions from cultured human TE cells indicates...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycop...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107169
更新日期:2017-04-01 00:00:00
abstract::Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, preferentially induces cell death in neoplastic epithelial cells types while sparing their normal counterparts. The effects of mda-7/IL-24 in acute myeloid leukemia (AML) cells have not been extensive...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.068007
更新日期:2010-12-01 00:00:00
abstract::Accumulated evidence suggests that dopamine and dopamine D1 agonists can activate phospholipase C in both brain and peripheral tissue. The receptor that mediates the hydrolysis of phosphoinositides has not been identified. The cloned dopamine D1A receptor that is generally thought to be linked to adenylyl cyclase, has...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.1.6
更新日期:1997-01-01 00:00:00
abstract::Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can gene...
journal_title:Molecular pharmacology
pub_type: 评论,杂志文章
doi:10.1124/mol.105.011429
更新日期:2005-04-01 00:00:00
abstract::We showed previously that subtypes of alpha 1-adrenergic receptors can be differentiated by selective inactivation with chlorethylclonidine (CEC) [Mol. Pharmacol. 32:505-510 (1987)] or by their affinities for the competitive antagonist WB 4101 [Nature (Lond.) 329:333-335 (1987)]. Examining eight rat tissues, the propo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.120.119909
更新日期:2020-07-01 00:00:00
abstract::We have expanded previous studies with the 5-hydroxytryptamine (5-HT)(2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-[(125)I]iodophenyl)-2-aminopropane [(+/-)-[(125)I]DOI] in human brain that had shown biphasic competition curves for several 5-HT(2A) receptor antagonists by using new selective antagonists of 5-HT(2A) (M...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::A series of isoflavone and tyrphostin compounds were found to inhibit the degradation of cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on the isoflavone structure were critical for PDE isozyme-selective inhibition. Replacement of the C-7 hydroxyl group of the isoflavone w...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.57.4.738
更新日期:2000-04-01 00:00:00