[KRP-297, MCC-555].
KRP-297 and MCC-555, which are being developed in Japan as thiazolidinediones, uniquely bind and activate peroxisome proliferator-activated receptors(PPAR). KRP-297, unlike other thiazolidinediones, effects on not only PPAR gamma but also PPAR alpha. Furthermore, this compound acts directly on basal glucose uptake in the rat skeletal muscle. KRP-297 decreased plasma glucose and insulin levels, and also blood triglyceride and free fatty acid in diabetic animal models. MCC-555 has significant antidiabetic properties yet its binding affinity for PPAR gamma is less than 1/10 that of BRL 49653. Thus, it is regarded now as a PPAR gamma modulator rather than agonist, depending on cell type. At present, clinical phase II studies of both drugs are under way.
Yamanouchi
T
T
Department of Internal Medicine, University of Teikyo.
D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050356:Lipid Metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D045162:Thiazolidinediones; D053778:Thiazolidines; D014157:Transcription Factors / Q000378:metabolism
D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D053778:Thiazolidines; D014157:Transcription Factors; C116017:5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide; D005947:Glucose; C115174:netoglitazone