CAY10566 is identified as a potent, orally bioavailable, and selective inhibitor of stearoyl-CoA desaturase1 (SCD1), exhibiting IC50s of 4.5 and 26 nM in mouse and human enzymatic assays, respectively. It also demonstrates strong cellular efficacy in HepG2 cells by inhibiting the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs, with an IC50 of 7.9 nM or 6.8 nM[1].[2].
体内研究
In vivo studies reveal that after the establishment of palpable tumors, treatment with CAY10566 at a dose of 2.5 mg/kg administered orally twice daily exhibits a more pronounced effect on Akt-driven tumors compared to Ras-driven tumors. The mean tumor volume, relative to untreated tumors by day 13 or 14 post-therapy, is significantly lower in the Akt-driven tumor group (0.5±0.04) than in the Ras-driven tumor group (0.67±0.05), with a P-value of 0.01 for the comparison between Ras and Akt-driven tumors as determined by a two-tailed t-test[4].
体外研究
Additionally, CAY10566 concentration-dependently reduces the proliferation of Swiss 3T3 cells over 24 hours, with a concentration range of 0.0001-10 μM[3].
To investigate the inhibitory effect of CAY10566 on SCD activity in MOVAS-1 cells and its impact on ER stearate levels and vascular calcification. Results showed that CAY10566 significantly inhibited SCD activity, increased ER stearate levels, and induced ATF4 expression and vascular calcification.
J Lipid Res. 2012 Aug;53(8):1543-52
synovial mesenchymal stem cells (MSCs)
2.5 µM
3 h
Inhibition of SCD1 activity, reduction of cell membrane fluidity, and increased tolerance to DMSO
Stem Cell Res Ther. 2022 May 3;13(1):177
human umbilical vein endothelial cells (HUVECs)
25 µM
3 h
Inhibition of SCD1 activity, reduction of cell membrane fluidity, and increased tolerance to DMSO
Stem Cell Res Ther. 2022 May 3;13(1):177
CAY10566 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
High-fat diet-induced NAFLD model
Intraperitoneal injection
7.5 mg/kg
Once every three days for 14 weeks
To investigate the effects of CAY10566 on high-fat diet-induced NAFLD in mice. Results showed that CAY10566 significantly ameliorated hepatic steatosis and lipid droplet accumulation, enhanced AMPK activity and lipophagy.
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