MCC-555 (Mitsubishi-Tokyo Pharmaceuticals).
Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing MCC-555, a thiazolidinedione peroxisome proliferation activated receptor (PPAR)-gamma agonist, as a potential treatment for type 2 diabetes [204644]. Johnson and Johnson is developing the compound outside of Japan [304271,322655]. As of March 2000, MCC-555 was in phase II trials as an insulin sensitizer, both in Japan and abroad [371091]. Phase I trials have been completed by Mitsubishi-Tokyo in the UK and Japan [304271]. Johnson and Johnson trials have shown that the drug is 3-fold more potent than rosiglitazone in the diabetic mouse model, KK-Ay. MCC-555 activates the PPARgamma target gene, aP2, with greater maximal efficacy than other agonists of this target [322655]. MCC-555 binds PPARgamma transcriptional activity which is highly context-specific, such that it can function as a full or partial agonist, or an antagonist, depending on the cell type or DNA binding site. These transcriptional properties are partially explained by unique partial agonism of coactivator recruitment to PPARgamma. This context-specific activity may contribute to its enhanced hypoglycemic potency in vivo despite reduced affinity for PPARgamma [335218]. In February 1999, ING Barings reported that Mitsubishi Chemical expected peak potential sales of yen100 billion for MCC-555, although analysts regarded this prediction as being excessively high at the time [405416].
Velussi
M
M
Monfalcone and Gorizia, Diabetology Department, Monfalcone, Italy. maveluss@tin.it