Aldometanib (LXY-05-029) is an orally active aldolase inhibitor that prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, useful in metabolic homeostasis research [1].

Aldometanib (0-1000 nM; 2 h) activates AMPK through preventing aldolase from binding to FBP to engender a pseudo-starvation signal [1]. Western Blot Analysis [1] Cell Line: Mouse primary hepatocytes, MEFs cells Concentration: 0-1000 nM Incubation Time: 2 h Result: Activated AMPK in mouse embryonic fibroblasts (MEFs) and mouse primary hepatocytes cells. Immunofluorescence [1] Cell Line: MEFs cells Concentration: 5 nM Incubation Time: 2 h Result: Inhibited TRPVs and induces AXIN lysosomal translocation.

Aldometanib, administered orally at dosages ranging from 0-10 mpk, effectively reduces blood glucose levels in lean mice and, when given at 2-10 mpk twice daily for a week, mitigates blood glucose and ameliorates fatty liver in obese hyperglycemic mice. Additionally, it addresses fatty liver and nonalcoholic steatohepatitis issues, and a regimen of 2 mpk twice daily over a month alleviates liver fibrosis in NASH mice. Moreover, Aldometanib extends the lifespan of C. elegans through the lysosomal pathway when administered orally at 0-50 μM for up to 50 days. In lean mice, dosages of 0-10 mpk lower fasting blood glucose, enhance glucose tolerance, and promote muscular TBC1D1 phosphorylation for glucose uptake. In obese hyperglycemic mice, a week-long administration of 2-10 mpk effectively lowers blood glucose, decreases hepatic TAG, and enhances insulin sensitivity through muscular AMPK dependencies, also diminishing fat mass. For NASH mice, a month-long administration of 2 mpk results in the reduction of NASH diagnostic histological scores, decreased hepatic cell apoptosis, reduced inflammatory liver responses, and improved glucose tolerance. In C. elegans, dosages of 0-50 μM improve oxidative stress resistance and bolster mitochondrial functions, while for C57BL/6 mice, administering 100 μg/mL orally rejuvenates muscle function and extends lifespan by increasing NAD+ levels and mitochondrial oxidative respiration.