AS1842856 | CAS#836620-48-5 | Foxo1inhibitor

MedKoo Cat#: 530424 | Name: AS1842856

Description:

WARNING: This product is for research use only, not for human or veterinary use.

AS1842856 is a cell-permeable Foxo1inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM. Targeting FoxO1 with AS1842856 suppresses adipogenesis. AS1842856 can be an anti-obesity agent that warrants further investigation.

Chemical Structure

AS1842856

CAS#836620-48-5

Theoretical Analysis

MedKoo Cat#: 530424

Name: AS1842856

CAS#: 836620-48-5

Chemical Formula: C18H22FN3O3

Exact Mass: 347.1645

Molecular Weight: 347.39

Elemental Analysis: C, 62.23; H, 6.38; F, 5.47; N, 12.10; O, 13.82

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

No Data

Synonym

AS1842856; AS-1842856; AS 1842856.

IUPAC/Chemical Name

5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

InChi Key

MOMCHYGXXYBDCD-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H22FN3O3/c1-2-22-9-11(18(24)25)17(23)14-13(22)8-12(15(19)16(14)20)21-10-6-4-3-5-7-10/h8-10,21H,2-7,20H2,1H3,(H,24,25)

SMILES Code

O=C(C1=CN(CC)C2=C(C(N)=C(F)C(NC3CCCCC3)=C2)C1=O)O

Appearance

White to light yellow solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A7K10C30

QC Data

View QC data: current batch, Lot#A7K10C30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

AS1842856 is a cell-permeable inhibitor that blocks the transcription activity of Foxo1 with IC50 of 33 nM.

In vitro activity:

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. Reference: Mol Pharmacol. 2010 Nov;78(5):961-70. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20736318

In vivo activity:

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. Reference: Mol Pharmacol. 2010 Nov;78(5):961-70. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20736318

	Solvent	mg/mL	mM
Solubility
	DMSO	5.0	14.39

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 347.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Nagashima T, Shigematsu N, Maruki R, Urano Y, Tanaka H, Shimaya A, Shimokawa T, Shibasaki M. Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol. 2010 Nov;78(5):961-70. doi: 10.1124/mol.110.065714. Epub 2010 Aug 24. PMID: 20736318. 2. He J, Zhang A, Song Z, Guo S, Chen Y, Liu Z, Zhang J, Xu X, Liu J, Chu L. The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt-FoxO1 pathway. Biosci Rep. 2019 May 10;39(5):BSR20190112. doi: 10.1042/BSR20190112. PMID: 30967498; PMCID: PMC6509061.

In vivo protocol:

1: Wang Q, Ren J. mTOR-Independent autophagy inducer trehalose rescues against insulin resistance-induced myocardial contractile anomalies: Role of p38 MAPK and Foxo1. Pharmacol Res. 2016 Sep;111:357-73. doi: 10.1016/j.phrs.2016.06.024. PubMed PMID: 27363949; PubMed Central PMCID: PMC5026602. 2: Liu L, Zheng LD, Zou P, Brooke J, Smith C, Long YC, Almeida FA, Liu D, Cheng Z. FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes. Cell Cycle. 2016 Aug 2;15(15):2033-41. doi: 10.1080/15384101.2016.1192732. PubMed PMID: 27260854; PubMed Central PMCID: PMC4968963. 3: Zhang Z, Amorosa LF, Coyle SM, Macor MA, Birnbaum MJ, Lee LY, Haimovich B. Insulin-Dependent Regulation of mTORC2-Akt-FoxO Suppresses TLR4 Signaling in Human Leukocytes: Relevance to Type 2 Diabetes. Diabetes. 2016 Aug;65(8):2224-34. doi: 10.2337/db16-0027. PubMed PMID: 27207509. 4: Chung S, Lee TJ, Reader BF, Kim JY, Lee YG, Park GY, Karpurapu M, Ballinger MN, Qian F, Rusu L, Chung HY, Unterman TG, Croce CM, Christman JW. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype. Oncotarget. 2016 Apr 5;7(14):17532-46. doi: 10.18632/oncotarget.8162. PubMed PMID: 27007158; PubMed Central PMCID: PMC4951231. 5: Diep CH, Knutson TP, Lange CA. Active FOXO1 Is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming. Mol Cancer Res. 2016 Feb;14(2):141-62. doi: 10.1158/1541-7786.MCR-15-0431. PubMed PMID: 26577046; PubMed Central PMCID: PMC4755896. 6: Tan P, Guan H, Xie L, Mi B, Fang Z, Li J, Li F. FOXO1 inhibits osteoclastogenesis partially by antagnozing MYC. Sci Rep. 2015 Nov 16;5:16835. doi: 10.1038/srep16835. PubMed PMID: 26568463; PubMed Central PMCID: PMC4645183. 7: Zhang L, Ji QH, Ruge F, Lane C, Morris D, Tee AR, Dayan CM, Ludgate M. Reversal of Pathological Features of Graves' Orbitopathy by Activation of Forkhead Transcription Factors, FOXOs. J Clin Endocrinol Metab. 2016 Jan;101(1):114-22. doi: 10.1210/jc.2015-2932. PubMed PMID: 26502358. 8: Lartey LJ, Werneck-de-Castro JP, O-Sullivan I, Unterman TG, Bianco AC. Coupling between Nutrient Availability and Thyroid Hormone Activation. J Biol Chem. 2015 Dec 18;290(51):30551-61. doi: 10.1074/jbc.M115.665505. PubMed PMID: 26499800; PubMed Central PMCID: PMC4683275. 9: Chien PT, Lin CC, Hsiao LD, Yang CM. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes. Toxicol Appl Pharmacol. 2015 Dec 1;289(2):349-59. doi: 10.1016/j.taap.2015.09.009. PubMed PMID: 26385185. 10: Pandey A, Kumar GS, Kadakol A, Malek V, Gaikwad AB. FoxO1 Inhibitors: The Future Medicine for Metabolic Disorders? Curr Diabetes Rev. 2016;12(3):223-30. Review. PubMed PMID: 26239835. 11: Karki S, Farb MG, Ngo DT, Myers S, Puri V, Hamburg NM, Carmine B, Hess DT, Gokce N. Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity. Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1498-506. doi: 10.1161/ATVBAHA.114.305139. PubMed PMID: 25908760; PubMed Central PMCID: PMC4441602. 12: Sakamoto K. [Conversion of pancreatic δ-cells into β-cells]. Nihon Yakurigaku Zasshi. 2015 Mar;145(3):164. doi: 10.1254/fpj.145.164. Japanese. PubMed PMID: 25765499. 13: Zou P, Liu L, Zheng L, Liu L, Stoneman RE, Cho A, Emery A, Gilbert ER, Cheng Z. Targeting FoxO1 with AS1842856 suppresses adipogenesis. Cell Cycle. 2014;13(23):3759-67. doi: 10.4161/15384101.2014.965977. PubMed PMID: 25483084; PubMed Central PMCID: PMC4613185. 14: Savai R, Al-Tamari HM, Sedding D, Kojonazarov B, Muecke C, Teske R, Capecchi MR, Weissmann N, Grimminger F, Seeger W, Schermuly RT, Pullamsetti SS. Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat Med. 2014 Nov;20(11):1289-300. doi: 10.1038/nm.3695. PubMed PMID: 25344740. 15: Trinité B, Chan CN, Lee CS, Mahajan S, Luo Y, Muesing MA, Folkvord JM, Pham M, Connick E, Levy DN. Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells. PLoS One. 2014 Oct 16;9(10):e110719. doi: 10.1371/journal.pone.0110719. PubMed PMID: 25330112; PubMed Central PMCID: PMC4199762. 16: Ju SJ, Zhao Y, Chang X, Guo L. Orexin A protects cells from apoptosis by regulating FoxO1 and mTORC1 through the OX1R/PI3K/AKT signaling pathway in hepatocytes. Int J Mol Med. 2014 Jul;34(1):153-9. doi: 10.3892/ijmm.2014.1769. PubMed PMID: 24807827. 17: Diep CH, Charles NJ, Gilks CB, Kalloger SE, Argenta PA, Lange CA. Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells. Cell Cycle. 2013 May 1;12(9):1433-49. doi: 10.4161/cc.24550. PubMed PMID: 23574718; PubMed Central PMCID: PMC3674071. 18: Nagashima T, Shigematsu N, Maruki R, Urano Y, Tanaka H, Shimaya A, Shimokawa T, Shibasaki M. Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol. 2010 Nov;78(5):961-70. doi: 10.1124/mol.110.065714. PubMed PMID: 20736318.