AS1842856

For research use only.

Catalog No.S8222

12 publications

AS1842856 Chemical Structure

CAS No. 836620-48-5

AS1842856 is a cell-permeable inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM. It could directly bind to the active Foxo1, but not the Ser256-phosphorylated form. AS1842856 suppresses autophagy.

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Selleck's AS1842856 has been cited by 12 publications

4 Customer Reviews

  • (E-F) Images and results from microfluidic devices containing human kidney capillaries from young healthy kidneys (n = 6 per group, 2 donors) (E) or aged hypertensive kidneys (n = 5 per group, 1 donor) (F), stimulated to undergo sprouting angiogenesis with VEGF. In the presence of the FOXO1 inhibitor AS1842856 both healthy capillaries and aged capillaries successfully form new capillaries with tip-stalk structures. FOXO1 inhibition enables angiogenic capacity in kidney MVECs like that seen in HUVECs. Capillaries engineered from aged hypertensive kidneys had a higher tendency to form new vascular structures, although these did not show tip cell morphology (F, lower left images). FOXO1 inhibition enhanced new vessel formation with obvious tip cell morphology. Note bpV was less effective in aged capillary.

    Biomaterials, 2017, 141:314-329. AS1842856 purchased from Selleck.

    (B) The effects of inactivating FOXO1 and Bcl2 on myoblast apoptosis. AnnexinV-FITC-PI detection method was employed for the detection of apoptotic cells by flow cytometry. PI was used as a counterstain to discriminate dead cells from apoptotic ones. The ratio of apoptotic cells was calculated based on AnnexinV and PI straining. Q1 represents the necrotic cell potion, Q2: apoptotic cells in the late stage; Q3: apoptotic cells in the early stage; Q4: normal cells. (C) The plot of cell proliferation analysis in different cell cycles. (D) The plot of cell apoptosis analysis in different stages. AS1842856 (FOXO1 inhibitor) and ABT199 (Bcl2 inhibitor) were utilized for specific knockdown of FOXO1 and Bcl2 activities in myoblast for 24 h at the concentration of 10 μM with equal volume of DMSO as control groups (n = 4). *P b 0.05; **P b 0.01.

    Biochim Biophys Acta Gene Regul Mech, 2017, 1860(6):674-684. AS1842856 purchased from Selleck.

  • AS1842856 treatment on the mRNA levels of gluconeogenic genes in Ad‐PANDER‐infected HepG2 cells.

    J Cell Mol Med, 2018, doi:10.1111/jcmm.14073. AS1842856 purchased from Selleck.

    The plot of cell proliferation analysis in different cell cycles. Foxo1 inhibitor: AS1842856

    Biochim Biophys Acta, 2017, 1860(6):674-684. AS1842856 purchased from Selleck.

Purity & Quality Control

Choose Selective FOX Inhibitors

Biological Activity

Description AS1842856 is a cell-permeable inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM. It could directly bind to the active Foxo1, but not the Ser256-phosphorylated form. AS1842856 suppresses autophagy.
Targets
Foxo1 [1]
(In HepG2 cells)
33nM
In vitro

AS1842856 predominantly suppresses Foxo1-mediated transactivation by directly binding to Foxo1. In HepG2 cells transiently transfected with a Foxo1 expression vector, AS1842856 potently represses Foxo1-mediated promoter activity in a dose-dependent manner similar to that seen in insulin treatment.AS1842856 administered at 0.1 μM inhibits Foxo3a- and Foxo4-mediated promoter activity by 3 and 20%, respectively. In contrast, Foxo1-mediated promoter activity is decreased by 70%. Foxo1 inhibitor AS1842856 may suppress endogenous G6Pase and PEPCK activities by decreasing their mRNA levels, which may lead to inhibition of glucose production in Fao cells[1].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
3T3L1 preadipocytes NF;KU|BHfW6ldHnvckBie3OjeR?= M13TO|EvOMLizszN MVmxNkBl[Xm| NX\j[FlMeGW{c3nzeIVvfCC2cnXheI1mdnRib3[gZ4VtdHNid3n0bEBCWzF6NEK4OVYhMGSjeYOgNE0yOiliYXztc5N1KGOxbYDs[ZRmdHlicILleoVvfGWmIITo[UBi\Gmyb3flcoV{cXN? MXWyOVQ5OzB6NB?=

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
p-JNK / JNK / p-P38 / P38 / p-ERK / ERK ; 

PubMed: 26568463     


Levels of p-JNK and p-P38 were increased by AS1842856 in RAW264.7 cells. After treatment with AS1842856 (at a concentration of 0.1, 0.5 or 1.0 μM) for 12 h, RAW264.7 cells were incubated with RANKL (50 ng/mL) for 30 min. Total proteins were then extracted for Western blot analysis. Antibodies to ACTB and total JNK, p38 and ERK served as loading controls.

FoxO1 / FoxO3a / FoxO4 ; 

PubMed: 30404794     


Detection of the FoxO1, FoxO3a, and FoxO4 proteins in iSLK-RGB-BAC16 cells treated with 0 (DMSO alone), 5, 7, and 10 μM FoxO1 inhibitor AS1842856 for 48 h. 

Sox2 / Musashi / Nestin / GFAP ; 

PubMed: 27448972     


Western blot analyses of stemness markers and GFAP after incubation with 10 μM of the FoxO inhibitor AS1842856.

26568463 30404794 27448972
In vivo Oral administration of AS1842856 to diabetic db/db mice leads to a drastic decrease in fasting plasma glucose level via the inhibition of hepatic gluconeogenic genes, whereas administration to normal mice has no effect on the fasting plasma glucose level. Treatment with AS1842856 also suppresses an increase in plasma glucose level caused by pyruvate injection in both normal and db/db mice[1].

Protocol

Cell Research:

[1]
- Collapse
  • Cell lines: Fao cells
  • Concentrations: 0, 0.1, 1, 10uM
  • Incubation Time: 30min
  • Method:

    Fao cells are serum-starved (1 h) and incubated for 30 min with either insulin or AS1842856 at the indicated concentration. Protein lysates are prepared from cells treated with either insulin or AS1842856, and relative concentration of phosphorylated Foxo1 protein is determined by Western blot analysis.


    (Only for Reference)
Animal Research:

[1]
- Collapse
  • Animal Models: db/db mice, ICR mice
  • Dosages: 100mg/kg
  • Administration: Oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 23 mg/mL (66.2 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 347.38
Formula

C18H22FN3O3
CAS No. 836620-48-5
Storage powder
in solvent
Synonyms N/A
Smiles CCN1C=C(C(=O)C2=C1C=C(C(=C2N)F)NC3CCCCC3)C(=O)O

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID