Mapracorat, a novel non-steroidal selective glucocorticoid receptor agonist for the treatment of allergic conjunctivitis.
Glucocorticoids are used to treat chronic and severe forms of allergic conjunctivitis. Although they exert a rapid and powerful therapeutic activity, relevant side effects may limit their ocular use: increase of intraocular pressure, cataract formation and reduced resistance to infections. New glucocorticoids displaying the same potency of classical glucocorticoids but with fewer adverse effects are needed for the treatment of ocular disorders. Mapracorat (also known as ZK245186 or BOL-303242-X) is a novel non-steroidal selective glucocorticoid receptor agonist that is in the first phases of clinical evaluation (Phase II Clinical trials) for topical treatment of inflammatory skin and ocular disorders. Mapracorat binds selectively to human glucocorticoid receptor and displays powerful anti-inflammatory effects. In experimental models of ocular diseases, mapracorat reduces clinical symptoms, eosinophil recruitment, chemokines and pro-inflammatory cytokines production at ocular level, confirming that it acts preventing both the early and late phase of allergic response. Interestingly, mapracorat induces a lower increase of intraocular pressure in comparison to the classical glucocorticoid dexamethasone. Several clinical trials are ongoing to investigate the efficacy and safety of mapracorat for the treatment of several ocular diseases. Transrepressive mechanisms are thought to account for the majority of mapracorat's antiinflammatory effects; however, the induction of anti-inflammatory proteins likely involved in transactivation events may contribute to mapracorat-mediated anti-inflammatory properties and deserve to be further investigated in suitable in vivo and in vitro models. These observations may influence how novel "differential" ligands are discovered, identified and evaluated.
Monica
M
Baiula
Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 40126 Bologna, Italy. santi.spampinato@unibo.it.
Santi
S
Spampinato
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D003233:Conjunctivitis, Allergic / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D023421:Models, Animal; D000439:Pentanols / Q000494:pharmacology* / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D015533:Transcriptional Activation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D016207:Cytokines; D000439:Pentanols; D011804:Quinolines; C546413:R-1,1,1-trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-(((2-methyl-5-quinolyl)amino)methyl)pentan-2-ol; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone