Group Of Selective Inhibitors Research Articles

Therapeutic potential of the treatment and control of severe recurrent atopic dermatitis

Atopic dermatitis is a hereditary inflammatory skin disease characterized by pruritus, a long recurrent course and certain evolutionary dynamics. Atopic dermatitis of moderate and severe severity is considered a systemic disease that exacerbates the course of associated pathologies, including cardiovascular, neuropsychiatric, and malignant diseases. The current paper presents the essentials about moderate and severe severity atopic dermatitis, statistical epidemiologic and pathogenetic data is thoroughly processed, the issues of the quality of life of such patients are especially accentuated. It is known that a few years ago the therapy of moderate and severe atopic dermatitis was based on systemic corticosteroids and classical immunosuppressants, but they had limited efficacy and were not suitable for long-term treatment due to their safety profile. This article highlights the development of new effective and easy-to-use therapies for atopic dermatitis, which led to the emergence of selective Janus kinase inhibitors. The review presents the way selective inhibitors of Janus kinases works and their effect on the barrier function of the skin. The paper provides the research data on the very first drug from the group of selective inhibitors - upadacitinib, which proved its efficacy on a par with a high degree of safety. The authors presented their own clinical observation of the use of upadacitinib in adolescents with severe atopic dermatitis. The use of upadacitinib in the described clinical cases led to a decrease in the severity of subjective and objective symptoms of inflammatory skin diseases.

Constrained search of conformational hyperspace of inactivators of glucosamine-6-phosphate synthase.

Glucosamine-6-phosphate (GlcN-6-P) synthase (EC 2.6.1.16) is a key enzyme in amino sugar metabolism in micro-organisms and its selective and irreversible inhibitors can become valuable antifungal drugs. We performed a constrained search of the conformational hyperspace of glutamine and of the set of specific inactivators of the enzyme, as well as of some non-specific inhibitors of many cysteine containing enzymes. From these calculations we obtained spatial relationships of functional groups, the presence and specific orientation of which in the active site of the enzyme is important for effective and selective action of the inhibitor. Subsequent quantum chemical calculations confirmed the correctness of the pharmacophore conformation we obtained. Pharmacophore conformation of FMDP molecule, the most potent inhibitor in the selective inhibitors group, is placed close to the energy minimum on the conformational energy map.