ZLN005 is a novel transcriptional regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). ZLN005 stimulates the expression of PGC-1α and downstream genes in skeletal muscle cells, improving glucose utilization and fatty acid oxidation at a concentration of 20 μM. ZLN005 increased PGC-1α and downstream gene transcription in skeletal muscle, whereas hepatic PGC-1α and gluconeogenesis genes were reduced. ZLN005 increased fat oxidation and improved the glucose tolerance, pyruvate tolerance, and insulin sensitivity of diabetic db/db mice. ZLN005 selectively elevated the expression of PGC-1α in myotubes and skeletal muscle and exerted promising therapeutic effects for treating type 2 diabetes.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 20 mg/mL|
|Source||Diabetes (2013). Figure 1. ZLN005|
|Cell Lines||HEK293 cells|
|Incubation Time||24 h|
|Results||The mRNA levels of GLUT4, NRF1, estrogen-related receptor a (ERRa), cytochrome c oxidase 5b (cox5b), and acyl-CoA oxidase were increased by ZLN005 (10 μmol/L).|
Novel small-molecule PGC-1α transcriptional regulator with beneficial effects on diabetic db/db mice.
Zhang LN, et al. Diabetes. 2013 Apr;62(4):1297-307. PMID: 23250358.
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