CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer.

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 Chem

authors

Lee HM,Golub LM,Cao J,Teronen O,Laitinen M,Salo T,Zucker S,Sorsa T

doi

10.2174/0929867013373660

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

257-60

issue

3

eissn

0929-8673

issn

1875-533X

journal_volume

8

pub_type

杂志文章
  • The 2-chlorotrityl resin: a worthy addition to the medicinal chemist's toolbox.

    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

    authors: Hoekstra WJ

    更新日期:2001-05-01 00:00:00

  • Fatty Acids and Effects on In Vitro and In Vivo Models of Liver Steatosis.

    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...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170518101334

    authors: Vergani L

    更新日期:2019-01-01 00:00:00

  • Stem Cell Transplant for Advanced Stage Liver Disorders: Current Scenario and Future Prospects.

    abstract:BACKGROUND:Chronic Liver Disorders (CLD), caused by the lifestyle patterns like alcoholism or by non-alcoholic fatty liver disease or because of virus-mediated hepatitis, affect a large population fraction across the world. CLD progresses into end-stage diseases with a high mortality rate. Liver transplant is the only ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666191004161802

    authors: Mahmood A,Seetharaman R,Kshatriya P,Patel D,Srivastava AS

    更新日期:2020-01-01 00:00:00

  • Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis.

    abstract::Advances in combinatorial chemistry, high-throughput screening, and molecular modeling have revolutionized the process of drug discovery in the pharmaceutical industry. Drug discovery efforts for the primary protozoal parasitic diseases of the developing world, malaria, leishmaniasis, and trypanosomiasis, have also be...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867003374615

    authors: Werbovetz KA

    更新日期:2000-08-01 00:00:00

  • Quinoline-based antifungals.

    abstract::Although the assortment of antifungal drugs is broad, the most commonly used agents have major drawbacks. Toxicity, serious side effects or the emergence of drug resistance are amongst them. New drugs and drug candidates under clinical trials do not guarantee better pharmacological parameters. These new medicines may ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710791163966

    authors: Musiol R,Serda M,Hensel-Bielowka S,Polanski J

    更新日期:2010-01-01 00:00:00

  • Molecular hybridization: a useful tool in the design of new drug prototypes.

    abstract::Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can result in compounds pres...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707781058805

    authors: Viegas-Junior C,Danuello A,da Silva Bolzani V,Barreiro EJ,Fraga CA

    更新日期:2007-01-01 00:00:00

  • Natural COX-2 inhibitors as promising anti-inflammatory agents: an update.

    abstract::COX-2, a key enzyme that catalyzed the rate-limiting steps in the conversion of arachidonic acid to prostaglandins, played a pivotal role in inflammatory process. Different from other family members, COX-2 was barely detectable in normal physiological conditions and highly inducible during acute inflammatory response ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867327999200917150939

    authors: Cui J,Jia J

    更新日期:2020-09-17 00:00:00

  • Synthesis and applications for unnatural sugar nucleotides.

    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:

    authors: Elhalabi JM,Rice KG

    更新日期:1999-02-01 00:00:00

  • Atrial remodeling and novel pharmacological strategies for antiarrhythmic therapy in atrial fibrillation.

    abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and there...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711796642373

    authors: Jost N,Kohajda Z,Kristóf A,Kovács PP,Husti Z,Juhász V,Kiss L,Varró A,Virág L,Baczkó I

    更新日期:2011-01-01 00:00:00

  • Taking advantage of viral immune evasion: virus-derived proteins represent novel biopharmaceuticals.

    abstract::In healthy individuals, natural and adaptive immune responses are able to control virus entry into the host. In particular, CD8(+)-mediated cytotoxicity, sustained by the intervention of CD4+ cells, represents the major key event leading to virus eradication. On the other hand, viruses are able to evade from host immu...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986706775476106

    authors: Amati L,Passeri ME,Lippolis A,Lio D,Caruso C,Jirillo E,Covelli V

    更新日期:2006-01-01 00:00:00

  • The atherosclerotic plaque vulnerability: focus on the oxidative and endoplasmic reticulum stress in orchestrating the macrophage apoptosis in the formation of the necrotic core.

    abstract::Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the last decades, the precise mechanisms underlying plaque destabilization are still unknown. The disruption of the plaque and the thrombosis in the lumen th...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867322666150311150829

    authors: Cominacini L,Garbin U,Mozzini C,Stranieri C,Pasini A,Solani E,Tinelli IA,Pasini AF

    更新日期:2015-01-01 00:00:00

  • The effect of ageing on cytochrome p450 enzymes: consequences for drug biotransformation in the elderly.

    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

    doi:10.2174/092986707780090981

    authors: Wauthier V,Verbeeck RK,Calderon PB

    更新日期:2007-01-01 00:00:00

  • The seemingly trivial yet challenging synthesis of poly(aminoester) dendrimers.

    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

    doi:10.2174/0929867311209025011

    authors: Wang Y,Quelever G,Peng L

    更新日期:2012-01-01 00:00:00

  • Effects of Resveratrol and Other Polyphenols on the Most Common Brain Age-Related Diseases.

    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

    doi:10.2174/0929867324666170724102743

    authors: Sarubbo F,Moranta D,Asensio VJ,Miralles A,Esteban S

    更新日期:2017-01-01 00:00:00

  • Small Molecules as Drugs to Upregulate Metastasis Suppressors in Cancer Cells.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/0929867325666180522090842

    authors: Wong KM,Song J,Saini V,Wong YH

    更新日期:2019-01-01 00:00:00

  • Chemical and genetic engineering strategies to improve the potency of pharmaceutical proteins and enzymes.

    abstract::Over the last decade there has been significant progress in understanding the molecular basis of disease processes. At the same time the technological advances in the area of genomics and the efforts in proteomics research have increased the possibility of discovering many proteins with defined therapeutic functions. ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986708785132924

    authors: Platis D,Labrou NE

    更新日期:2008-01-01 00:00:00

  • Aminoacyl-tRNA synthetase inhibitors as potent antibacterials.

    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

    doi:10.2174/092986712801323199

    authors: Lv PC,Zhu HL

    更新日期:2012-01-01 00:00:00

  • (99m)Tc-radiolabelled peptides for tumour imaging: present and future.

    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

    pub_type: 杂志文章

    doi:10.2174/092986710791859388

    authors: Bolzati C,Refosco F,Marchiani A,Ruzza P

    更新日期:2010-01-01 00:00:00

  • Molecular probes for P2X7 receptor studies.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/092986707780831023

    authors: Gunosewoyo H,Coster MJ,Kassiou M

    更新日期:2007-01-01 00:00:00

  • Oxazolidinones as Anti-tubercular Agents: Discovery, Development and Future Perspectives.

    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

    doi:10.2174/0929867323666151106125759

    authors: Jadhavar PS,Vaja MD,Dhameliya TM,Chakraborti AK

    更新日期:2015-01-01 00:00:00

  • Photobiostimulation on wound healing treatment by ClAlPc-nanoemulsion from a multiple-wavelength portable light source on a 3D-human stem cell dermal equivalent.

    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

    pub_type: 杂志文章

    doi:10.2174/092986712803530502

    authors: Primo FL,de Paula LB,de Siqueira-Moura MP,Tedesco AC

    更新日期:2012-01-01 00:00:00

  • Homocysteine and cerebral ischemia: pathogenic and therapeutical implications.

    abstract::Homocysteine is a thiol aminoacid synthesized during the metabolism of methionine. Increased plasma levels of homocysteine can be the result of mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine-beta synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR). Addition...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707779941140

    authors: Pezzini A,Del Zotto E,Padovani A

    更新日期:2007-01-01 00:00:00

  • Enzyme Inhibitors as the Attractive Targets for the Treatment of Various Diseases.

    abstract:: ...

    journal_title:Current medicinal chemistry

    pub_type: 社论

    doi:10.2174/092986732618190821115641

    authors: Orhan IE

    更新日期:2019-01-01 00:00:00

  • Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug.

    abstract::Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth. Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common. Clinical resistance to camptothecins is still a poorly under...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867311320120006

    authors: Beretta GL,Gatti L,Perego P,Zaffaroni N

    更新日期:2013-01-01 00:00:00

  • Non peptidic alphavbeta3 antagonists: recent developments.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/0929867053363522

    authors: Cacciari B,Spalluto G

    更新日期:2005-01-01 00:00:00

  • In Silico Drug Repositioning for Chagas Disease.

    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

    doi:10.2174/0929867326666191016114839

    authors: Bellera CL,Alberca LN,Sbaraglini ML,Talevi A

    更新日期:2020-01-01 00:00:00

  • Protein Post-Translational Modification Crosstalk in Acute Myeloid Leukemia Calls for Action.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666190503164004

    authors: Hernandez-Valladares M,Wangen R,Berven FS,Guldbrandsen A

    更新日期:2019-01-01 00:00:00

  • Structure and ligand based drug design strategies in the development of novel 5- LOX inhibitors.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/092986712801661112

    authors: Aparoy P,Reddy KK,Reddanna P

    更新日期:2012-01-01 00:00:00

  • Targeting leukocytes in immune glomerular diseases.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/092986708783503230

    authors: Kitching AR,Holdsworth SR,Hickey MJ

    更新日期:2008-01-01 00:00:00

  • Protein-ligand docking in the new millennium--a retrospective of 10 years in the field.

    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...

    journal_title:Current medicinal chemistry

    pub_type: 历史文章,杂志文章,评审

    doi:10.2174/0929867311320180002

    authors: Sousa SF,Ribeiro AJ,Coimbra JT,Neves RP,Martins SA,Moorthy NS,Fernandes PA,Ramos MJ

    更新日期:2013-01-01 00:00:00