2222094-18-8

BC1618, an orally active Fbxo48 inhibitory compound, stimulates Ampk-dependent signaling (via preventing activated pAmpkα from Fbxo48-mediated degradation). BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity[1].

BC1618, an orally active Fbxo48 inhibitory compound, stimulates Ampk-dependent signaling (via preventing activated pAmpkα from Fbxo48-mediated degradation). BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity[1]. BC1618 enhances pAmpkα protein stability during CHX treatment[1].BC1618 displays more than 1,000-fold enhanced activity to stimulate pAmpkα in cells than metformin[1].BC1618 (0.1-2 μM, 16 h) induced dose- and time-dependent increases in pAmpkα and pACC protein levels are also confirmed in human primary-like hepatocytes[1].BC1618 (1 μM) effectively disrupts the interaction between Fbxo48 and pAmpkα, and has no effect on Fbxo48, Ampkα1 or Ampkα2 messenger RNAs[1].BC1618 increases the abundance of a series of autophagic marker proteins during glucose depletion. BC1618 induces phosphorylation of the mTORC1 associated protein Raptor, reducing pS6 levels, all consistent with the known mTOR inhibitory effects exerted by activated Ampk[1]. BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity in high-fat-diet-induced obese mice[1].BC1618, appears to be ~1,000-fold more potent than metformin and is extremely well tolerated in mice[1].BC1618 displays excellent oral bioavailability with a peak of 2,000 ng/mL within 0.5h and 500 ng/mL in plasma at 4h after an oral load of 20mg/kg[1].

[1]. Yuan Liu, et al. A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance. Nat Chem Biol. 2021 Mar;17(3):298-306.