tcsc2189 ZLN005

ZLN005 is a novel transcriptional regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).

IC50 value:

Target: PGC-1α

in vitro: ZLN005 increases expression of the PGC-1α gene in L6 myotubes. ZLN005 increased PGC-1α mRNA levels in a dose-dependent manner; 20 μmol/L ZLN005 caused a threefold increase over the control after 24 h. At 10 μmol/L, the PGC-1α mRNA levels were increased to almost the same extent at 16 to 48 h [1]. ZLN005 did not increase the expression of the PGC-1α gene in rat primary hepatocytes. AMP-activated protein kinase is involved in the mechanism inducing PGC-1α in L6 myotubes [1]

in vivo: An insulin tolerance test revealed that treatment with ZLN005 significantly decreased insulin resistance in db/db mice, as evidenced by the approximately 18% decrease in the AUC. A PTT also was performed in db/db mice, and ZLN005 improved pyruvate tolerance, as evidenced by the 16% decrease in the AUC. In db/db mice, plasma NEFA and triglyceride levels were decreased by 20% and 37%, respectively, and cholesterol was decreased by 10% with ZLN005 treatment. Plasma insulin and β-hydroxybutyrate content, liver/bodyweight index and adipose composition, and muscle and liver triglyceride levels, however, were not ameliorated by treatment with ZLN005 or metformin [1].