BC1618, an orally active compound that inhibits Fbxo48, induces Ampk-dependent signaling by preventing the degradation of activated pAmpkα mediated by Fbxo48. BC1618 enhances mitochondrial fission, promotes autophagy, and enhances hepatic insulin sensitivity [1].
体内研究
BC1618 enhances mitochondrial fission, promotes autophagy, and enhances hepatic insulin sensitivity in high-fat-diet-induced obese mice [1].
BC1618 appears to be approximately 1,000-fold more potent than metformin and is highly tolerated in mice [1].
BC1618 exhibits outstanding oral bioavailability, reaching a peak concentration of 2,000 ng/mL within 0.5 hours and maintaining a level of 500 ng/mL in plasma at 4 hours following an oral dose of 20 mg/kg [1].
体外研究
BC1618 increases the stability of pAmpkα protein during treatment with CHX [1].
BC1618 exhibits over 1,000-fold greater activity in stimulating pAmpkα in cells compared to metformin [1].
BC1618 (0.1-2 μM, 16 h) elicited dose- and time-dependent elevations in pAmpkα and pACC protein levels, as observed in human primary-like hepatocytes [1].
BC1618 (1 μM) efficiently disrupts the interaction between Fbxo48 and pAmpkα, without affecting the messenger RNAs of Fbxo48, Ampkα1, or Ampkα2 [1].
BC1618 enhances the levels of various autophagic marker proteins during glucose depletion. Additionally, BC1618 induces phosphorylation of Raptor, a protein associated with mTORC1, leading to decreased levels of pS6, which is in line with the recognized mTOR inhibitory effects induced by activated Ampk [1].
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