CAS 304896-28-4|AGK2

Introduction：Basic information about CAS 304896-28-4|AGK2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. AGK2 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Articles12
6. Synonyms

Common Name	AGK2
CAS Number	304896-28-4	Molecular Weight	434.274
Density	1.4±0.1 g/cm3	Boiling Point	675.1±55.0 °C at 760 mmHg
Molecular Formula	C₂₃H₁₃Cl₂N₃O₂	Melting Point	/
MSDS	USA	Flash Point	362.1±31.5 °C

Names

Name	2-Cyano-3-[[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide
Synonym	More Synonyms

AGK2 BiologicalActivity

Description	AGK2 is a selective SIRT2 inhibitor with IC50 of 3.5 μM. AGK2 can also inhibit SIRT1 and SIRT3 with IC50 of 30 and 91 μM, respectively.
Related Catalog	Research Areas >>Cancer
Target	SIRT2:3.5 μM (IC50) SIRT1:30 μM (IC50) SIRT3:91 μM (IC50)
In Vitro	AGK2 significantly inhibits cell proliferation in a dose-dependent manner. AGK2 also significantly inhibits cell growth in a dose-dependent manner without inducing cytotoxicity at low doses. Twelve days after AGK2 (5 μM) treatment, cells show a significantly reducing colony forming ability in soft agar to 46% of the control cells. Western blot analysis shows that the levels of CDK4 or CDK6 and cyclin D1 are decreased after AGK2 treatment in a dose-dependent manner. In addition, AGK2 inhibits the expression of p53 protein[2]. Treatment of microglial BV2 cells with 10 μM AGK2 leads to a significant increase in PAR signals. Treatment of microglial BV2 cells with 10 μM AGK2 also leads to a significant decrease in the intracellular ATP and significant increases in both late-stage apoptosis and necrosis of the cells[3].
In Vivo	AGK2 significantly reduces mortality and decreases levels of cytokines in blood (TNF-α: 298.3±24.6 vs 26.8±2.8 pg/mL, p=0.0034; IL-6: 633.4±82.8 vs 232.6±133.0 pg/mL, p=0.0344) and peritoneal fluid (IL-6: 704.8±67.7 vs 391.4±98.5 pg/mL, p=0.033) compare to vehicle control. AGK2 also suppresses the TNF-α and IL-6 production in the culturing splenocytes (TNF-α: 68.1±6.4 vs 23.9±2.8 pg/mL, p=0.0009; IL-6: 73.1±4.2 vs 49.6±3.0 pg/mL; p=0.0051)[4].
Cell Assay	Cells are exposed to different concentrations of AGK2 in 1 mL of 0.3% basal medium agar containing 10% FBS. The cultures are maintained at 37°C in a 5% CO2 incubator for 10-15 days, and the cell colonies are scored using an inverted microscope[2].
Animal Admin	Mice are intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2 h later subjects to CLP. Survival is monitored for 240 hours. AGK2-treating mice are grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritoneal fluid and peripheral blood are examined at 24 and 48 hours for cytokine production[4].
References	[1]. Tatum PR, et al. Identification of novel SIRT2-selective inhibitors using a click chemistry approach. Bioorg Med Chem Lett. 2014 Apr 15;24(8):1871-4. [2]. Kim HW, et al. Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability. Oncol Rep. 2016 Jan;35(1):235-42. [3]. Li Y, et al. Poly(ADP-ribose) polymerase mediates both cell death and ATP decreases in SIRT2 inhibitor AGK2-treated microglial BV2 cells. Neurosci Lett. 2013 Jun 7;544:36-40. [4]. Zhao T, et al. Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model. Curr Mol Med. 2015;15(7):634-41.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	675.1±55.0 °C at 760 mmHg
Molecular Formula	C₂₃H₁₃Cl₂N₃O₂
Molecular Weight	434.274
Flash Point	362.1±31.5 °C
Exact Mass	433.038483
PSA	78.92000
LogP	5.39
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.718
InChIKey	SVENPFFEMUOOGK-SDNWHVSQSA-N
SMILES	N#CC(=Cc1ccc(-c2cc(Cl)ccc2Cl)o1)C(=O)Nc1cccc2ncccc12
Storage condition	Room temp
Water Solubility	DMSO: soluble2mg/mL, clear (warmed)

Safety Information

Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes	Xi: Irritant;
Risk Phrases	36
Safety Phrases	26
RIDADR	NONH for all modes of transport

Articles12

Functionalized tetrahydro-1H-pyrido[4,3-b]indoles: a novel chemotype with Sirtuin 2 inhibitory activity.

Eur. J. Med. Chem. 92 , 145-55, (2015)

Sirtuins are protein deacylases with regulatory roles in metabolism and stress response. Functionalized tetrahydro-1H-pyrido[4,3-b]indoles were identified as preferential sirtuin 2 inhibitors, with in...

SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages.

Biochem. Biophys. Res. Commun. 450(4) , 1363-9, (2014)

SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory proc...

Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging.

EMBO J. 33(12) , 1321-40, (2014)

Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain...

Synonyms

ARC 239 dihydrochloride

(2E)-2-cyano-3-[5-(2,5-dichlorophenyl)furan-2-yl]-N-(quinolin-5-yl)prop-2-enamide

(2E)-2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furyl]-N-(5-quinolinyl)acrylamide

AGK2

2-Propenamide, 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-, (2E)-

(2E)-2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furyl]-N-(quinolin-5-yl)acrylamide

2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide

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