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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
The forkhead box protein O1 (Foxo1) is a transcription factor that plays a critical role in hepatic gluconeogenesis. AS-1842856 is a Foxo1 inhibitor with an IC50 value of 0.03μM. In HepG2 cells transiently transfected with vectors carrying human Foxo1, AS-1842856 inhibited Foxo1 activity in a dose-dependent manner. AS-1842856 at a concentration of 0.1μM decreased Foxo1-mediated transactivation by 70%. Treatment of Fao cells with AS-1842856 for 18 hours inhibited the mRNA expression of G6Pase and PEPCK with IC50 values of 0.13μM and 0.037μM, respectively. Treatment of Fao cells with AS-1842856 (0.1 – 10μM) alone or in combination with insulin (0.1 – 10nM) did not affect the phosphorylation state of Akt, ERK, or S6K. In ICR mice, oral administration of AS-1842856 (100mg/kg) at three time points (8AM, 6PM, and 8AM on the second day) during 26-h fasting significantly reduced the mRNA expression of G6Pase and PEPCK in the liver, but did not alter the plasma glucose level.[3]
作用机制
AS-1842856 inhibits Foxo1-mediated transactivation by directly binding to Foxo1.[3]
AS1842856 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow-derived macrophages (BMDMs)
5 μM
1 h
FOXO1 inhibitor significantly attenuated LPS-induced mRNA expression levels of Tnf and Il1b in BMDMs
Aging Cell. 2023 Oct;22(10):e13968.
neonatal rat cardiomyocytes (NRCMs)
1 μM
4 h
To evaluate the effect of AS1842856 on DOX-induced Rbl2 expression, results showed that AS1842856 inhibited Rbl2 expression.
JACC CardioOncol. 2023 Mar 28;5(3):360-373.
RAW264.7 cells
10 μM
48 h
AS1842856 dramatically inhibited ARG-1 expression and promoted iNOS expression, indicating that FoxO1 plays a key role in TGF-β-induced macrophage M2-like polarization
Stem Cell Res Ther. 2019 Nov 26;10(1):345.
mouse peritoneal macrophages
10 μM
48 h
AS1842856 dramatically inhibited ARG-1 expression and promoted iNOS expression, indicating that FoxO1 plays a key role in TGF-β-induced macrophage M2-like polarization
Stem Cell Res Ther. 2019 Nov 26;10(1):345.
BMDMs
58 nM
overnight
AS1842856 suppressed CD11c expression
iScience. 2023 Jul 11;26(8):107293.
THP-1
58 nM
overnight
AS1842856 suppressed CD11c expression
iScience. 2023 Jul 11;26(8):107293.
HL-60
58 nM
overnight
AS1842856 suppressed CD11c expression
iScience. 2023 Jul 11;26(8):107293.
human kidney microvascular endothelial cells (KMVECs)
0.5 μM
1 h
To evaluate whether FOXO1 inhibition could restore angiogenesis, the results showed that FOXO1 inhibition significantly promoted the formation of new vessels.
Biomaterials. 2017 Oct;141:314-329.
human umbilical vein endothelial cells (HUVECs)
0.5 μM
1 h
To evaluate the effect of FOXO1 inhibition on angiogenesis, the results showed that FOXO1 inhibition significantly promoted the formation of new vessels.
Biomaterials. 2017 Oct;141:314-329.
AS1842856 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Retinal ischemia-reperfusion injury model
Intraperitoneal injection
10 mg/kg
4 consecutive days, starting 1 day before modeling
AS1842856 inhibited FoxO1, alleviated RGC loss and retinal electrophysiological dysfunction induced by RIR injury, and protected retinal function by inhibiting autophagy activation.
Invest Ophthalmol Vis Sci. 2025 Feb 3;66(2):58
Mice
18-month-old aged mice
Oral gavage
10 mg/kg
Daily for 5 weeks
FOXO1 inhibitor significantly improved glucose homeostasis, liver fat accumulation, and systemic inflammation in old mice, and attenuated pro-inflammatory responses in hepatic macrophages
Aging Cell. 2023 Oct;22(10):e13968.
Mice
C57BL/6 and C57BL/Ks db/db mice
Intraperitoneal injection
30 μg/g
Single dose, lasting 60 minutes
To investigate the effect of AS1842856 on Foxo1 transcription in mouse liver, the results showed that AS1842856 eliminated 50-AMP-induced hepatic gluconeogenesis.
J Biol Chem. 2021 Jul;297(1):100846
C57BL/6 mice
Iron deficiency model
Intraperitoneal injection, Gavage
10 mg/kg, 20 mg/kg, 50 mg/kg
Daily, every 5 days, for one month
To evaluate the reversal effect of AS1842856 on bone mass reduction in iron-deficient mice
Cell Mol Life Sci. 2024 Aug 19;81(1):360.
Mice
DOX-induced cardiotoxicity model
Oral gavage
100 mg/kg
Twice daily for 2 days immediately after each DOX injection
To evaluate the effect of AS1842856 on DOX-induced Rbl2 expression, results showed that AS1842856 inhibited Rbl2 expression.
JACC CardioOncol. 2023 Mar 28;5(3):360-373.
Mice
High-fat diet-induced atherosclerosis model
Intraperitoneal injection
20 mg/kg
5 days a week for 8 weeks
AS1842856 notably suppressed atherosclerosis and decreased CD11c expression on monocytes
iScience. 2023 Jul 11;26(8):107293.
Mice
Ischemia reperfusion injury (IRI) model
Oral gavage
100 mg/kg
3 times a day for 5 days
To evaluate the effect of FOXO1 inhibition on microvascular regeneration and organ function, the results showed that FOXO1 inhibition significantly improved microvascular regeneration and kidney function.
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