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].
BC1618 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BEAS-2B cells
10 μM
5 h
Promoted mitochondrial fission observed via Mito Tracker staining and confocal microscopy
Nat Chem Biol. 2021 Mar;17(3):298-306
MDA-MB-468 cells
10 μM
48 h
To evaluate the effect of BC1618 on tumor cell growth. Results showed that BC1618 did not affect the growth or proliferation of tumor cells.
Adv Sci (Weinh). 2025 Apr;12(14):e2409835
CAR-T cells
10 μM
48 h
To evaluate the enhancement of BC1618 on the antitumor activity of CAR-T cells. Results showed that BC1618 significantly strengthened the antitumor response of CAR-T cells.
Adv Sci (Weinh). 2025 Apr;12(14):e2409835
Huh-7 human hepatic cells
30 µM
24 h
To evaluate the effect of BC1618 on GDF15 mRNA levels, results showed that BC1618 significantly increased GDF15 mRNA levels more than metformin.
Molecules. 2023 Jul 17;28(14):5468
BC1618 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
High fat diet-induced obese mice
Oral gavage
20 mg/kg
Two doses, 2 hours apart
Improved hepatic insulin sensitivity and reduced insulin-stimulated hepatic glucose production
Nat Chem Biol. 2021 Mar;17(3):298-306
NCG mice
Triple-negative breast cancer model
Intratumoral injection
10 μM
Single injection, observed for 20 days
To evaluate the antitumor effect of BC1618 combined with hydrogel-delivered CAR-T cells in vivo. Results showed that BC1618 significantly enhanced the antitumor activity of CAR-T cells.
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