Abstract：
:Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that play a critical role in the destruction of extracellular matrix proteins and, the shedding of membrane-bound receptor molecules in various forms of arthritis and other diseases. Under normal conditions, MMP, ADAM and ADAMTS gene expression aids in the maintenance of homeostasis. However, in inflamed synovial joints characteristic of rheumatoid arthritis and osteoarthritis. MMP, ADAM and ADAMTS production is greatly increased under the influence of pro-inflammatory cytokines. Analyses based on medicinal chemistry strategies designed to directly inhibit the activity of MMPs have been largely unsuccessful when these MMP inhibitors were employed in animal models of rheumatoid arthritis and osteoarthritis. This is despite the fact that these MMP inhibitors were largely able to suppress pro-inflammatory cytokine-induced MMP production in vitro. A focus on ADAM and ADAMTS inhibitors has also been pursued. Thus, recent progress has identified the "sheddase" activity of ADAMs as a viable target and the development of GW280264X is an experimental ADAM17 inhibitor. Of note, a monoclonal antibody, GLPG1972, developed as an ADAMTS-5 inhibitor, entered a Phase I OA clinical trial. However, the failure of many of these previously developed inhibitors to move beyond the preclinical testing phase has required that novel strategies be developed that are designed to suppress both MMP, ADAM and ADAMTS production and activity.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Malemud CJdoi
10.1016/j.bcp.2019.02.033subject
Has Abstractpub_date
2019-07-01 00:00:00pages
33-40eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30081-4journal_volume
165pub_type
杂志文章,评审abstract：:A method to evaluate interactions between biologically active agents is presented. Synergism, zero interaction, and antagonism were easily detected with the three-dimensional approach proposed herein. This method is compatible with a checkerboard design to diagnose the interaction between agents and obviate the need t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(95)02230-9
更新日期：1996-03-08 00:00:00
abstract：:The ability of adrenergic catechol derivatives, including dobutamine, dopamine, and isoproterenol, to inhibit lipid peroxidation was examined. All the catechol derivatives we tested strongly inhibited lipid peroxidation. Dobutamine was a more powerful inhibitor of iron-catalyzed lipid peroxidation than the other agent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00075-6
更新日期：1998-06-15 00:00:00
abstract：:Dihydromyricetin (DMY) is the most abundant flavonoid in Ampelopsis grossedentata possessing many pharmacological activities. But less is known about its protective effect against nonalcoholic steatohepatitis (NASH) in the context of metabolic syndrome. The present study is aimed to evaluate the pharmacological effect...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113927
更新日期：2020-05-01 00:00:00
abstract：:Dinucleotides of adenosine and thymidine in the ApnT series (n = 3,4,5 and 6) and their corresponding phosphonate analogues, where a methylene group replaces the oxygen between the alpha and beta phosphorus atoms adjacent to thymidine, have been evaluated as inhibitors of human leukaemic thymidylate kinase (dTMP kinas...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90141-4
更新日期：1988-02-15 00:00:00
abstract：:Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00343-7
更新日期：1996-08-23 00:00:00
abstract：:Synthetic ether lipids (EL) exert their antiproliferative action on leukemic cells through localization in the plasma membrane with subsequent biochemical effects which are still being elucidated. In the present study, the modulation of membrane-linked ATPase activity was investigated in relation to changes in membran...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90246-f
更新日期：1992-02-18 00:00:00
abstract：:N-Nitrosoguanidines are potential carcinogens. However, the toxicity of these agents is attenuated significantly in laboratory rodents by processes that remove the nitroso group to generate the relatively innocuous parent guanidinium compound. The denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine (CyanoDMNG) me...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00861-1
更新日期：1997-05-09 00:00:00
abstract：:Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.08.001
更新日期：2006-11-15 00:00:00
abstract：:Ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) is strongly hypoglycaemic in fasted normal and diabetic rats [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia 22, 456 (1982)]. POCA was fed for 12 weeks to rats on a standard low-fat (3%) diet at levels of 0.05% and 0.2% to give daily intakes of abou...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90242-9
更新日期：1984-02-01 00:00:00
abstract：:Hepatic microsomal preparations from male and female rats were delipidated by column chromatography following cholate solubilisation. The enzyme activities were reconstituted using known lipids and the vesicle reconstitution method. Enzyme activity was assayed using lignocaine as the substrate for the mixed function o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90071-2
更新日期：1987-04-15 00:00:00
abstract：:Pretreatment of NG108-15 cells with 0.03-25 microM prostaglandin E1 (PGE1) produced decreases in the maximal stimulation of adenylate cyclase activity produced by iloprost, N-ethylcarboxamidoadenosine and sodium fluoride. The rate of desensitization to all three agents was dependent on the concentration of PGE1 used, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90405-7
更新日期：1994-03-15 00:00:00
abstract：:2-Chloroacetaldehyde (CAA)-induced cytotoxicity in isolated hepatocytes was enhanced markedly if hepatocyte alcohol or aldehyde dehydrogenase was inhibited prior to CAA addition. Hepatocyte GSH depletion, ATP depletion and lipid peroxidation by CAA were also enhanced markedly. Furthermore, CAA was about 10- and 70-fol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90374-3
更新日期：1994-08-30 00:00:00
abstract：:The effect of ethanol abuse on the lipid ordering of the human erythrocyte membranes was studied by steady-state and time-resolved fluorescence anisotropy measurements of DPH and its polar analogue TMA-DPH, which probe different membrane regions. Steady-state anisotropy values with DPH as a probe were slightly but sig...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90062-7
更新日期：1988-10-15 00:00:00
abstract：:The nitroderivative 1-nitro-2-phenylethane (NPE) was recently described as a compound possessing heme-dependent soluble guanylyl cyclase (sGC) stimulating properties in vascular smooth muscle cells. In this study, we tested such pharmacological property of NPE in mice pancreatic acinar cells subjected to the bile salt...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.07.030
更新日期：2014-09-15 00:00:00
abstract：:Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.03.044
更新日期：2004-09-15 00:00:00
abstract：:It is thought that the oxidation of low density lipoprotein (LDL) plays a key role in the pathogenesis of atherosclerosis. It is well known that lipid peroxidation reactions are propagated by peroxyl radicals and it follows, therefore, that the capacity of an individual LDL particle to scavenge these oxidants may be a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90189-4
更新日期：1993-06-09 00:00:00
abstract：:The abilities of the naturally occurring polyamines, putrescine, spermidine and spermine, to affect variables related to the bioenergetic functions of isolated rat liver mitochondria were studied. At concentrations comparable to those present intracellularly, the polyamines inhibited state 4 respiration, but they had ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90654-2
更新日期：1982-12-15 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：:The vasoactive urotensin-II (UII), a cyclic undecapeptide widely distributed in cardiovascular, renal and endocrine systems, specifically binds the UII receptor (UT receptor), a G protein-coupled receptor (GPCR). The involvement of this receptor in numerous pathophysiological conditions including atherosclerosis, hear...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.08.023
更新日期：2014-11-15 00:00:00
abstract：:We have studied the effect of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)), two reactive oxygen species (ROS) on histamine release (HR) from RBL-2H3 cells, a rat mucosal-type mast cell line. Marked HR was elicited by antigen (DNP-HSA), calcium ionophore A23187, sodium fluoride or phospholipase C, but not with co...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00770-5
更新日期：2001-12-01 00:00:00
abstract：:In model experiments using human erythrocytes, glycochenodeoxycholate caused extensive membrane damage (as judged by release of membrane phospholipid and acetylcholinesterase and by cell lysis) at approximately 10-fold lower concentrations than glycocholate. Chenodeoxycholate feeding had no effect upon the total prote...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90660-9
更新日期：1984-07-15 00:00:00
abstract：:The challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer's disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different pati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2015.07.027
更新日期：2015-10-15 00:00:00
abstract：:To investigate the importance of NAD(P)H:quinone oxidoreductase 1 (or DT-diaphorase; NQO1) in the bioactivation of antitumor quinones, we established a series of stably transfected cell lines derived from BE human colon adenocarcinoma cells. BE cells have no NQO1 activity due to a genetic polymorphism. The new cell li...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00631-1
更新日期：2001-06-15 00:00:00
abstract：:Azithromycin is considered an effective drug to treat the perinatal mycoplasma infection. However, there is a lack of studies on developmental toxicity of azithromycin. In this study, we observed the developmental toxicity of fetal liver induced by prenatal azithromycin exposure (PAE) in mice and explored the potentia...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114130
更新日期：2020-10-01 00:00:00
abstract：:The present study addressed the question of whether the number of myocardial beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidaz...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00164-1
更新日期：1999-09-01 00:00:00
abstract：:Corticosteroid esters have been encapsulated into intact erythrocytes and used as an intravenous treatment for adjuvant induced arthritis in the rat. The treatment consisted of injections of the encapsulated steroids with the effects monitored for up to 14 days. On an equivalent weight basis both encapsulated cortisol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90362-3
更新日期：1983-11-15 00:00:00
abstract：:Elevated glucose levels in diabetes mellitus is associated with increased oxidized low density lipoprotein (oxLDL). High glucose (HG) and oxLDL are key inducers of oxidative stress and inflammatory processes responsible for diabetic vascular disorders. Rosmarinic acid is a polyphenol with antioxidant, anti-inflammator...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114246
更新日期：2020-12-01 00:00:00
abstract：:In this study, 1,4,6-androstatriene-3,17-dione (ATD) was demonstrated to cause time-dependent loss of aromatase activity in rat ovarian microsomes in vitro. In vivo, an injection of ATD caused inhibition of ovarian aromatase and reduced estrogen secretion in pregnant mare's serum gonadotropin-primed rats for at least ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90415-4
更新日期：1982-06-01 00:00:00
abstract：:Suramin, a drug intensively used in the chemotherapy of African trypanosomiasis and onchocerciasis, is currently being tested in clinical trials for AIDS treatment. Its effects on mitochondrial energy metabolism in mammals were studied. At low concentrations it inhibited ATP synthesis and ATPase activity in submitocho...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90241-9
更新日期：1988-07-01 00:00:00
abstract：:The capacity of cultured bovine adrenal medullary cells to metabolize and export cyclic AMP has been studied. Basal cellular cyclic AMP levels were increased 50% by 100 microM 3-isobutyl-1-methylxanthine (IBMX) and rolipram, a class IV (cyclic AMP-specific) phosphodiesterase (PDE) inhibitor. They were not affected by ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90335-g
更新日期：1992-12-01 00:00:00
