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
Keywords: Allergic conjunctivitis, apoptosis, chemokines, cytokines, eosinophil, glucocorticoid, glucocorticoid receptor,
mapracorat, mast cell, transactivation, transrepression.
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