AGK-2 | SIRT2 inhibitor | CAS#304896-28-4

MedKoo Cat#: 526063 | Name: AGK-2

Description:

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

AGK-2 is a potent and selective inhibitor of sirtuin 2 (SIRT2).

Chemical Structure

AGK-2

CAS#304896-28-4

Theoretical Analysis

MedKoo Cat#: 526063

Name: AGK-2

CAS#: 304896-28-4

Chemical Formula: C23H13Cl2N3O2

Exact Mass: 433.0385

Molecular Weight: 434.28

Elemental Analysis: C, 63.61; H, 3.02; Cl, 16.33; N, 9.68; O, 7.37

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
1g	USD 3,950.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Synonym

AGK-2; AGK2; AGK 2

IUPAC/Chemical Name

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

InChi Key

SVENPFFEMUOOGK-SDNWHVSQSA-N

InChi Code

InChI=1S/C23H13Cl2N3O2/c24-15-6-8-19(25)18(12-15)22-9-7-16(30-22)11-14(13-26)23(29)28-21-5-1-4-20-17(21)3-2-10-27-20/h1-12H,(H,28,29)/b14-11+

SMILES Code

O=C(NC1=C2C=CC=NC2=CC=C1)/C(C#N)=C/C3=CC=C(C4=CC(Cl)=CC=C4Cl)O3

Appearance

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

Instruction

View handling instruction

Biological target:

AGK2 is a selective SIRT2 inhibitor with an IC50 of 3.5 μM. AGK2 inhibits SIRT1 and SIRT3 with IC50s of 30 and 91 μM, respectively.

In vitro activity:

To elucidate the effect of AGK2 on hepatitis B virus replication in vitro, the HepAD38 cells were treated with AGK2 at the concentration of 10μM, and Entecavir (25nM) was used as positive control. After treatment for seven days, total RNAs and 3.5kb RNA was extracted and subjected to real-time PCR. The HBV RNAs include 0.7kb X mRNA, 2.4kb and 2.1kb surface protein mRNAs, 3.5kb precore (pc) RNA and pregenomic (pg) RNA. Interestingly, AGK2 decreased HBV 3.5kb and total RNAs in HepAD38 cells (Fig. 2A-2B). Consistently, Northern blot confirmed that AGK2 inhibited HBV 3.5kb and 2.4/2.1kb RNAs. (Fig. 2C). Real-time PCR and Southern blot also showed that HBV DNA replicative intermediates in cells were reduced (Fig. 2D-2E). Furthermore, HBV core protein (HBc) was detected by Western blot, and the expression levels of HBsAg and HBeAg in cell supernatants were determined by ELISA. Consistently, AGK2 also inhibited the HBc expression, as well as HBsAg and HBeAg secretions. (Fig. 2F-2H). Reference: Int J Med Sci. 2018; 15(12): 1356–1364. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158674/

In vivo activity:

In AGK2 group, liver tissues shown slight tissue damage compared with control group. However, TAA group displayed massive hemorrhagic necrosis, liver lobules with disturbed architecture, remarkable inflammatory cells infiltration. Whereas, in AGK2 + TAA group, the hepatocyte necrosis was improved obviously, and the numbers of infiltrative inflammatory cells were significantly reduced (Fig. 1A). Similarly, the histological score of liver in AGK2 + TAA group was lower than TAA group (Fig. 1B). In addition, the 24 h survival rate of TAA-induced mice was observed in each group. The results showed that 86.7% of mice survived in AGK2 + TAA group, whereas only 60.0% in TAA group (Fig. 1C). Finally, this study assessed the plasma levels of hepatic enzymes in each group. TAA group showed significant increases in levels of ALT and AST. However, treatment with AGK2 significantly decreased the abnormal increase of AST and ALT levels (Fig. 1D, E). Reference: Life Sci. 2019 Aug 1;230:68-75. https://pubmed.ncbi.nlm.nih.gov/31129140/

	Solvent	mg/mL	mM
Solubility
	DMSO	5.7	13.06
	DMF	3.0	6.91
	DMF:PBS (pH 7.2) (1:2)	0.3	0.69

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 434.28 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:

1. Jiao F, Wang Y, Zhang W, Zhang H, Chen Q, Wang L, Shi C, Gong Z. AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1. J Neuroimmune Pharmacol. 2020 Jun;15(2):196-208. doi: 10.1007/s11481-019-09890-x. Epub 2019 Nov 30. PMID: 31786712. 2. Yu HB, Jiang H, Cheng ST, Hu ZW, Ren JH, Chen J. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int J Med Sci. 2018 Sep 7;15(12):1356-1364. doi: 10.7150/ijms.26125. PMID: 30275764; PMCID: PMC6158674. 3. Kim YY, Hur G, Lee SW, Lee SJ, Lee S, Kim SH, Rho MC. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway. Pharmacol Res. 2020 Sep;159:105027. doi: 10.1016/j.phrs.2020.105027. Epub 2020 Jun 18. PMID: 32565308. 4. Jiao FZ, Wang Y, Zhang WB, Zhang HY, Chen Q, Shi CX, Wang LW, Gong ZJ. Protective role of AGK2 on thioacetamide-induced acute liver failure in mice. Life Sci. 2019 Aug 1;230:68-75. doi: 10.1016/j.lfs.2019.05.061. Epub 2019 May 23. PMID: 31129140.

In vitro protocol:

In vivo protocol:

1. Kim YY, Hur G, Lee SW, Lee SJ, Lee S, Kim SH, Rho MC. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway. Pharmacol Res. 2020 Sep;159:105027. doi: 10.1016/j.phrs.2020.105027. Epub 2020 Jun 18. PMID: 32565308. 2. Jiao FZ, Wang Y, Zhang WB, Zhang HY, Chen Q, Shi CX, Wang LW, Gong ZJ. Protective role of AGK2 on thioacetamide-induced acute liver failure in mice. Life Sci. 2019 Aug 1;230:68-75. doi: 10.1016/j.lfs.2019.05.061. Epub 2019 May 23. PMID: 31129140.

1: Kumar V, Spangenberg O, Konrad M. Cloning of the guanylate kinase homologues AGK-1 and AGK-2 from Arabidopsis thaliana and characterization of AGK-1. Eur J Biochem. 2000 Jan;267(2):606-15. doi: 10.1046/j.1432-1327.2000.01045.x. PMID: 10632732. 2: Liu QY, Zhuang Y, Song XR, Niu Q, Sun QS, Li XN, Li N, Liu BL, Huang F, Qiu ZX. Tanshinone IIA prevents LPS-induced inflammatory responses in mice via inactivation of succinate dehydrogenase in macrophages. Acta Pharmacol Sin. 2021 Jun;42(6):987-997. doi: 10.1038/s41401-020-00535-x. Epub 2020 Oct 7. PMID: 33028985; PMCID: PMC8149828. 3: Shimizu K, Quillinan N, Orfila JE, Herson PS. Sirtuin-2 mediates male specific neuronal injury following experimental cardiac arrest through activation of TRPM2 ion channels. Exp Neurol. 2016 Jan;275 Pt 1(Pt 1):78-83. doi: 10.1016/j.expneurol.2015.10.014. Epub 2015 Oct 30. PMID: 26522013; PMCID: PMC5193101. 4: Mai A. Small-molecule chromatin-modifying agents: therapeutic applications. Epigenomics. 2010 Apr;2(2):307-24. doi: 10.2217/epi.10.7. PMID: 22121876. 5: Biella G, Fusco F, Nardo E, Bernocchi O, Colombo A, Lichtenthaler SF, Forloni G, Albani D. Sirtuin 2 Inhibition Improves Cognitive Performance and Acts on Amyloid-β Protein Precursor Processing in Two Alzheimer's Disease Mouse Models. J Alzheimers Dis. 2016 Jun 30;53(3):1193-207. doi: 10.3233/JAD-151135. PMID: 27372638. 6: Scuderi C, Stecca C, Bronzuoli MR, Rotili D, Valente S, Mai A, Steardo L. Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer's disease. Front Pharmacol. 2014 May 13;5:89. doi: 10.3389/fphar.2014.00089. PMID: 24860504; PMCID: PMC4027795. 7: Rotili D, Tarantino D, Nebbioso A, Paolini C, Huidobro C, Lara E, Mellini P, Lenoci A, Pezzi R, Botta G, Lahtela-Kakkonen M, Poso A, Steinkühler C, Gallinari P, De Maria R, Fraga M, Esteller M, Altucci L, Mai A. Discovery of salermide- related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. J Med Chem. 2012 Dec 27;55(24):10937-47. doi: 10.1021/jm3011614. Epub 2012 Dec 12. PMID: 23189967. 8: Kumar V. Cloning and sequence analysis of lily and tobacco guanylate kinases. Mol Biol Rep. 2000 Mar;27(1):45-9. doi: 10.1023/a:1007131013675. PMID: 10939525.