Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: A hypoxia specific mechanism of action

2013 ◽  
Vol 58 (4) ◽  
pp. 280-291 ◽  
Author(s):  
Aneta Radziwon-Balicka ◽  
Corey Ramer ◽  
Cesar Moncada de la Rosa ◽  
Barbara Zielnik-Drabik ◽  
Paul Jurasz
Keyword(s):  
Mechanism Of Action ◽  
Specific Mechanism

Propeptides as modulators of functional activity of proteases

2010 ◽  
Vol 1 (3-4) ◽  
pp. 305-322 ◽  
Author(s):  
Ilya V. Demidyuk ◽  
Andrey V. Shubin ◽  
Eugene V. Gasanov ◽  
Sergey V. Kostrov
Keyword(s):  
Mechanism Of Action ◽  
Functional Activity ◽  
Protein Function ◽  
Living Organism ◽  
Biological Properties ◽  
Biological Mechanism ◽  
Structural Elements ◽  
Specific Mechanism ◽  
Catalytic Domains ◽  
Cognate Protein

AbstractMost proteases are synthesized in the cell as precursor-containing propeptides. These structural elements can determine the folding of the cognate protein, function as an inhibitor/activator peptide, mediate enzyme sorting, and mediate the protease interaction with other molecules and supramolecular structures. The data presented in this review demonstrate modulatory activity of propeptides irrespective of the specific mechanism of action. Changes in propeptide structure, sometimes minor, can crucially alter protein function in the living organism. Modulatory activity coupled with high variation allows us to consider propeptides as specific evolutionary modules that can transform biological properties of proteases without significant changes in the highly conserved catalytic domains. As the considered properties of propeptides are not unique to proteases, propeptide-mediated evolution seems to be a universal biological mechanism.

The role and effects of carnosine and β-alanine on exercise: an updated mini review

2014 ◽  
Vol 44 (2) ◽  
pp. 127-133 ◽  
Author(s):  
E. Lily ◽  
D. Papandreou
Keyword(s):  
Mechanism Of Action ◽  
Exercise Performance ◽  
Design Methodology ◽  
Strong Support ◽  
Specific Mechanism ◽  
Muscle Carnosine ◽  
Content Type

Purpose – The paper aims to describe the role and effects of carnosine and β-alanine on exercise. Design/methodology/approach – The review includes the most updated studies found in Pub-Med all of which are in relation to carnosine and β-alanine on exercise performance. Findings – The use of β-alanine in recent research has shown to increase muscle carnosine concentrations in as short as two weeks, with increasing levels with longer supplementation periods. Although there is strong support that β-alanine supplementation during training possesses ergogenic value, the specific mechanism of action and ergogenic value remains to be fully examined. Originality/value – The paper gives information to nutritionists, clinical dietitians and sports nutritionists on the newest data about the role and effects of carnosine and β-alanine on exercise performance.

scholarly journals Setting the scene – a future ‘epidemic’ of immune-related adverse events in association with checkpoint inhibitor therapy

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii1-vii6 ◽  
Author(s):  
Maria V Bermudez ◽  
Sophie Papa
Keyword(s):  
Adverse Events ◽  
Mechanism Of Action ◽  
Inflammatory Disease ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Specific Mechanism ◽  
Future Developments ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Abstract Cancer immune therapy with checkpoint inhibitors (CPIs) has changed the landscape of treatment for a growing number of indications. These drugs are associated with a specific mechanism of action that has profound implications for both immunology and inflammatory disease. This article looks to set the scene covering the history of CPI therapy to date and outlining the likely future developments.

scholarly journals Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII

2019 ◽  
Vol 20 (5) ◽  
pp. 1208 ◽  
Author(s):  
Kerem Buran ◽  
Silvia Bua ◽  
Giulio Poli ◽  
F. Önen Bayram ◽  
Tiziano Tuccinardi ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Carbonic Anhydrase ◽  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Carbonic Anhydrase Ix ◽  
Specific Mechanism ◽  
Single Digit ◽  
Molecular Modeling Studies ◽  
Human Carbonic Anhydrase ◽  
Substituted Coumarins

A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.

Synthesis and Activity of Putative Small-Molecule Inhibitors of the F-Box Protein SKP2

2015 ◽  
Vol 68 (4) ◽  
pp. 660 ◽  
Author(s):  
Andrew E. Shouksmith ◽  
Laura E. Evans ◽  
Deborah A. Tweddle ◽  
Duncan C. Miller ◽  
Elaine Willmore ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Hela Cells ◽  
Preliminary Data ◽  
Chiral Auxiliaries ◽  
Specific Mechanism ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
A Cell ◽  
Inhibitory Activities ◽  
F Box Protein

The tetrahydropyran 4-(((3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline was reported to disrupt the SCFSKP2 E3 ligase complex. Efficient syntheses of this tetrahydropyran derivative and analogues, including the des-dimethyl derivative 4-(((3-(tetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline, are described. The enantiomers of the des-dimethyl compound were obtained using Evans’ chiral auxiliaries. Structure–activity relationships for these tetrahydropyrans and analogues have been determined by measurement of growth-inhibitory activities in HeLa cells, which indicated a non-specific mechanism of action that correlates with inhibitor lipophilicity. However, preliminary data with (R)- and (S)-4-(((3-(tetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline showed enantioselective inhibition of the degradation of p27 in a cell-based assay that acts as a reporter of SKP2 activity.

scholarly journals Of the available triptans, which should be chosen and how should they be used?

2019 ◽  
pp. 29-31
Author(s):  
Marcelo Moraes Valença ◽  
Emanuela Paz Rosas ◽  
Raisa Ferreira Costa ◽  
Amanda Araújo da Silva ◽  
Maria Rosana de Souza Ferreira ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Mechanism Of Action ◽  
Research Priorities ◽  
Clinical Scenario ◽  
Pharmacological Effects ◽  
Specific Mechanism ◽  
Optimal Form ◽  
Amount Of Information ◽  
Enormous Amount

There is a plethora of articles dealing with the use of triptans to treat migraine, but so far no unanimity exists regarding the optimal form of using this group of drugs in a patient with recurrent attacks of migraine. Although all of them may exert their pharmacological effects through a known specific mechanism of action, i.e. agonist effects on serotonin 5-HT (1B/1D) receptors, distinct differences exist. The author comment a few facts on the prescription of triptans and possible adverse effects, depending on the clinical scenario. Thus, even though an enormous amount of information has accumulated over the last few decades on triptans, several questions remain to be answered, and research priorities need to be addressed.

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