Abstract:
:Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown. CMT-3 (6-demethyl, 6-deoxy, 4-dedimethylamino TC) has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study. Confluent MT1-MMP transfected COS-1 cells were harvested, washed thoroughly, subjected to N(2) cavitation and cell membrane enriched fractions were isolated by sequential centrifugations. This MT1-MMP preparation exhibited (i) pro-MMP-2 activating activity as shown by molecular weight shift of this gelatinase from 72 kDa to 62 kDa using gelatin zymography, and (ii) the ability to degrade both [(3)H-methyl] gelatin and casein at 37 degrees C. Adding CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness (using the Matrigel system) of HT-1080 fibrosarcoma cells. The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Lee HM,Golub LM,Cao J,Teronen O,Laitinen M,Salo T,Zucker S,Sorsa Tdoi
10.2174/0929867013373660subject
Has Abstractpub_date
2001-02-01 00:00:00pages
257-60issue
3eissn
0929-8673issn
1875-533Xjournal_volume
8pub_type
杂志文章abstract::The polystyrene-based 2-chlorotrityl resin was originally used in the synthesis of peptides using an Fmoc-amino acid/carboxyl-linked protocol. While traditionally employed to prepare a number of biologically active peptides, the resin has received increasing attention as a support for the synthesis of pseudopeptide an...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013373192
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperl...
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更新日期:2007-01-01 00:00:00
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abstract::The synthesis and biological evaluation of carbohydrate mimetics has begun to more clearly define the diverse roles of carbohydrates in nature. Often the strategy invoves the design and synthesis of glycosyltransferase and glycosidase inhibitors both as tools to elucidate the mechanism of action of these enzymes and a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-02-01 00:00:00
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journal_title:Current medicinal chemistry
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journal_title:Current medicinal chemistry
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更新日期:2015-01-01 00:00:00
abstract::Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
abstract::Poly(aminoester) dendrimers are expected to hold great promise as biodegradable nanocarriers for drug delivery due to their advantageous properties allowing their biodegradability, potentially lower toxicity and possibility of diverse chemical conjugations. The synthetic strategies for constructing such dendrimers inc...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:With global increase in elderly population, modern societies must find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. Th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::It is well-recognized that the majority of cancer-related deaths is attributed to metastasis, which can arise from virtually any type of tumor. Metastasis is a complex multistep process wherein cancer cells must break away from the primary tumor, intravasate into the circulatory or lymphatic systems, extravasate, prol...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2008-01-01 00:00:00
abstract::The emergence of bacterial strains with resistance to currently marketed antibacterial agents has spurred interest in the discovery of new antibacterial agents with novel modes of action. One set of potential novel targets are the family of bacterial aminoacyltRNA synthetases (AaRS). Aminoacyl-tRNA synthetases are the...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::Receptor-binding peptides have attracted an enormous interest in targeting molecules for the development of tumour specific radiopharmaceutical compounds. The overexpression of many receptors on human tumour makes such peptide-ligands attractive agents for diagnostic imaging and therapy of cancers. The use of solid-ph...
journal_title:Current medicinal chemistry
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更新日期:2010-01-01 00:00:00
abstract::The ionotropic P2X7 receptor (P2X7R) has become the focus of intense research interest for a number of reasons: i) it is a cation selective ion channel that is modulated by extracellular ATP. Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable to hydrophilic mol...
journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract::TB drug development pipeline represents varied structural classes of molecules. Oxazolidinones represent synthetic anti-bacterial agents with unique mechanism of action having wide spectrum of activity, oral bioavailability and well established SAR. They act by inhibiting translation at the initiation phase of protein...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::This research evaluated the effect of multiple-wave lasertherapy on the healing process of surgical wounds based on in vitro models denominated stem-dermal equivalents. These human skin models were obtained from a co-culture of dermal cells and bone marrow mesenchymal stem cells. The experimental tests were carried ou...
journal_title:Current medicinal chemistry
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更新日期:2012-01-01 00:00:00
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journal_title:Current medicinal chemistry
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abstract:: ...
journal_title:Current medicinal chemistry
pub_type: 社论
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journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
abstract::The alphavbeta3 receptor, which are members of the group of the cellular adhesion molecules (CAM), are heterodimeric transmembrane glycoprotein receptors involved in processes such as cell-cell and cell-matrix adhesion, cell migration and signaling. Integrin alphavbeta3 receptor is expressed on almost all cells origin...
journal_title:Current medicinal chemistry
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更新日期:2005-01-01 00:00:00
abstract::Chagas disease is an infectious tropical disease included within the group of neglected tropical diseases. Though historically endemic to Latin America, it has lately spread to high-income countries due to human migration. At present, there are only two available drugs, nifurtimox and benznidazole, approved for this t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Post-translational modification (PTM) crosstalk is a young research field. However, there is now evidence of the extraordinary characterization of the different proteoforms and their interactions in a biological environment that PTM crosstalk studies can describe. Besides gene expression and phosphorylation ...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform asso...
journal_title:Current medicinal chemistry
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更新日期:2012-01-01 00:00:00
abstract::The glomerulonephritides are a collection of separate diseases with differing pathogeneses that collectively are common and important causes of renal disease. Effective, non-toxic immunomodulatory treatments for glomerulonephritis are lacking. This review will focus on our understanding of the role of leukocytes in im...
journal_title:Current medicinal chemistry
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更新日期:2008-01-01 00:00:00
abstract::Protein-ligand docking is currently an important tool in drug discovery efforts and an active area of research that has been the subject of important developments over the last decade. These are well portrayed in the rising number of available protein-ligand docking software programs, increasing level of sophisticatio...
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更新日期:2013-01-01 00:00:00