Cyclosporins are cyclic polypeptide macrolides that were originally derived from the soil fungus Tolypocladium inflatum. Cyclosporine (also known as cyclosporine A) was discovered by Sandoz and developed for the tretment of immune disorders. The drug was approved by FDA for such diseases as Rheumatoid Arthritis, Psoriasis (Neoral), Keratoconjunctivitis sicca (Restasis) and prevention of transplant rejections (Neoral and Sandimmune). Cyclosporine’s primary immunosuppressive mechanism of action is inhibition of T-lymphocyte function. Upon administration cyclosporine binds to cyclophilin A and thus inhibits calcineurin, leading to immune system suppression.

2S,4R ketoconazole or levoketoconazole is the 2S,4R enantiomer of ketoconazole, purified from racemic ketoconazole. Both enantiomers exerts antifungal activity. Ketoconazole activates AhR in gene reporter cell line and dose-dependently induces CYP1A1 mRNA and CYP1A1 protein in HepG2 cells, with enantiospecific pattern, i.e. 2R,4S ketoconazole was much more active as compared to 2S,4R ketoconazole. Levoketoconazole was shown to be a more potent inhibitor than the 2R,4S enantiomer of several enzymes in the steroidogenic pathway (CYP11B1, CYP17 and CYP21). Levoketoconazole was tested for the treatment of endogenous Cushing’s syndrome (Phase III) and type 2 diabetes mellitus (Phase II).

Enisoprost is a prostaglandin E1 analog. Enisoprost exerts immunosuppressive activity and gastric antisecretory effect. Enisoprost was being studied for the treatment of peptic ulcer and transplant rejection. Enisoprost development has been discontinued.