Repositioning Candidate Details
| Candidate ID: | R0318 |
| Source ID: | DB14596 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Loteprednol etabonate |
| Synonyms: | Loteprednol etabonate |
| Molecular Formula: | C24H31ClO7 |
| SMILES: | [H][C@@]12CC[C@](OC(=O)OCC)(C(=O)OCCl)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C |
| Structure: |
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| DrugBank Description: | Loteprednol Etabonate (LE) is a topical corticoid anti-inflammatory. It is used in ophthalmic solution for the treatment of steroid responsive inflammatory conditions of the eye such as allergic conjunctivitis, uveitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, and selected infective conjunctivitides. As a nasal spray, it can be used for the treatment and management of seasonal allergic rhinitis. Most prescription LE products, however, tend to be indicated for the treatment of post-operative inflammation and pain following ocular surgery . A number of such new formulations that have been approved include Kala Pharmaceutical's Inveltys - the first twice-daily (BID) ocular corticosteroid approved for this indication, designed specifically to enhance patient compliance and simplified dosing compared to all other similar ocular steroids that are dosed four times daily . Moreover, LE was purposefully engineered to be a 'soft drug', one that is designed to be active locally at the site of administration and then rapidly metabolized to inactive components after eliciting its actions at the desired location, thereby subsequently minimizing the chance for adverse effects . |
| CAS Number: | 82034-46-6 |
| Molecular Weight: | 466.96 |
| DrugBank Indication: | A number of prescription loteprednol etabonate ophthalmic products are specifically indicated for the treatment of post-operative inflammation and pain following ocular surgery . |
| DrugBank Pharmacology: | Loteprednol etabonate (LE) belongs to a unique class of corticosteroids with potent anti-inflammatory effects designed to be active at the site of action . Animal studies have shown that LE has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone . This particular class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body . Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity . Specifically, LE is an ester derivative of one of these analogs, cortienic acid etabonate . In particular, LE possesses a metabolically labile 17 beta-chloromethyl ester function which was designed in order to be hydrolyzed to an inactive carboxylic acid moiety . This inactive metabolite is more hydrophilic and is thus readily eliminated from the body . LE also exhibits good ocular permeation properties and good skin permeation properties . |
| DrugBank MoA: | Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing . They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly associated with inflammation . While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established . Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms . In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins . It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid . Arachidonic acid is released from membrane phospholipids by phospholipase A2 . The use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery . |
| Targets: | Glucocorticoid receptor 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 |
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