scholarly journals Selective protein unfolding: a universal mechanism of action for the development of irreversible inhibitors

2018 ◽  
Vol 54 (14) ◽  
pp. 1738-1741 ◽  
Author(s):  
Samuel Askin ◽  
Thomas E. H. Bond ◽  
Alanna E. Sorenson ◽  
Morgane J. J. Moreau ◽  
Helma Antony ◽  
...  
Keyword(s):  
High Throughput ◽  
Mechanism Of Action ◽  
Protein Unfolding ◽  
Enzyme Inhibitors ◽  
Irreversible Inhibitors ◽  
Differential Scanning Fluorimetry ◽  
Universal Mechanism

Selective protein unfolding was combined with high-throughput differential scanning fluorimetry of GFP-tagged proteins for the identification of irreversible enzyme inhibitors.

Enzyme inhibitors of microbial origin

1980 ◽  
Vol 290 (1040) ◽  
pp. 291-301 ◽  
Keyword(s):  
Enzyme Inhibitors ◽  
Future Research ◽  
Main Interest ◽  
Porcine Pancreas ◽  
The Past ◽  
Microbial Origin ◽  
Irreversible Inhibitors ◽  
Antibiotic Agents ◽  
Potential Use ◽  
New Metabolites

The screening for enzyme inhibitors of microbial origin in the past decades has been a prosperous area to find new metabolites that are of potential importance as therapeutic or antibiotic agents. This review attempts a survey of recent achievements in this type of screening. Special emphasis is given to enzyme inhibitors and screening systems in fields where industry has a main interest in development. This includes some notes on the improved methodology for the detection of reversible and irreversible inhibitors of β-lactamases and the presentation of a unique inhibitor of α-amylase from porcine pancreas isolated from a strain of Streptomyces tendae . This inhibitor (HOE 467) may be of potential use in the treatment of diabetic conditions, obesity and adipositas. The results show that the screening for enzyme inhibitors from microorganisms still provides one of the central challenges for future research.

Targeting histidine for developing a new generation of covalent enzyme inhibitors

2021 ◽  
Vol 17 ◽  
Author(s):  
Donald Poirier
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Drug Development ◽  
Chemical Bond ◽  
Amino Acid Residue ◽  
Enzyme Inhibitors ◽  
Irreversible Inhibitors ◽  
Covalent Inhibitors ◽  
Targeted Inhibitors ◽  
New Generation

: Despite the significant number of irreversible inhibitors developed over the years, strong prejudices remain for this type of therapeutic molecule, particularly in the area of drug development. New generations of covalent targeted inhibitors are, however, in development, and interest is increasingly growing. In fact, the new generation of covalent inhibitors has a weakly reactive species (warhead) that is able, in a particular context, to selectively form a chemical bond with a given amino acid residue, which can be irreversible or reversible. In addition to new selective warheads, new amino acids are also targeted. In the following text, we will focus on covalent targeted inhibitors that selectively alkylate histidine.

Molecule which changed the view on skin treatment

2021 ◽  
pp. 44-55
Author(s):  
L.Ya. Fedorich
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Local Treatment ◽  
Mechanisms Of Action ◽  
Clinical Effects ◽  
Topical Retinoids ◽  
Acne Therapy ◽  
Universal Mechanism

Objective — to study the modern classification, mechanisms of action and clinical effects of vitamin A derivatives, to analyze retinoid for local treatment of various dermatoses with a universal mechanism of action at the epidermis and dermis levels. Materials and methods. A review of the literature and an analysis of the results of international clinical trials of drugs based on the natural retinoid of the first generation — tretinoin (retinoic acid) is presented. The works of dozens of authors since 1980s to the present day are analyzed. Most sources provide detailed information on the results of topical retinoids in acne therapy, which are the base of clinical guidelines. Long-term (6 months or more) studies of retinoic acid-based preparations carried out in recent decades have discovered the unique clinical effects of tretinoin in the treatment of skin photoaging, actinic keratosis, etc. They are achieved due to the effect of tretinoid on the nuclear receptors of keratinocytes and fibroblasts. Results and discussion. The molecular mechanisms of action of retinoic acid, realizing the cellular and tissue effects of the most studied retinoid, are systematized and grouped in a single review. It has been proven that a unique feature of tretinin is its ability to activate directly all subtypes of RARs- and, indirectly, RARs-nuclear receptors of skin cells. A new modern drug for external use is presented — AltrenoТМ lotion containing micronized 0.05 % tretinoin in combination with sodium hyaluronate, soluble collagen and glycerin. This combination exhibits the expected clinical efficacy in acne therapy and prevents side effects such as dryness, redness and exfoliation. AltrenoТМ is approved for use in children of 9 years of age and older. Conclusions. Tretinoin (retinoic acid) is a modern powerful retinoid with a universal mechanism of action, recommended for the treatment of acne.

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