Repositioning Candidate Details

Candidate ID: R0384
Source ID: DB01047
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Fluocinonide
Synonyms: Fluocinonide
Molecular Formula: C26H32F2O7
SMILES: [H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)COC(C)=O
Structure:
DrugBank Description: A topical glucocorticoid used in the treatment of eczema.
CAS Number: 356-12-7
Molecular Weight: 494.5249
DrugBank Indication: A topical anti-inflammatory product for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
DrugBank Pharmacology: Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It mediates its effects to relieve itching, redness, dryness, crusting, scaling, inflammation, and discomfort associated with inflammatory skin conditions.
DrugBank MoA: Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. Fluocinonide binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Like other glucocorticoid agents Fluocinolone acetonide acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen). It also promotes the breakdown of lipids (lipolysis), and proteins, leading to the mobilization of extrahepatic amino acids and ketone bodies. This leads to increased circulating glucose concentrations (in the blood). There is also decreased glycogen formation in the liver.
Targets: Glucocorticoid receptor agonist; Smoothened homolog agonist
Inclusion Criteria: Therapeutic strategy associated

Strategy ID Strategy Synonyms Related Targets Related Drugs
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class