AGK2 (SIRT2 inhibitor)

AGK2 (SIRT2 inhibitor)
Clinical data
Drug classSirtuin 2 (SIRT2) inhibitor
Identifiers
  • (E)-2-cyano-3-[5-(2,5-dichlorophenyl)furan-2-yl]-N-quinolin-5-ylprop-2-enamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.164.349
Chemical and physical data
FormulaC23H13Cl2N3O2
Molar mass434.28 g·mol−1
3D model (JSmol)
  • C1=CC2=C(C=CC=N2)C(=C1)NC(=O)/C(=C/C3=CC=C(O3)C4=C(C=CC(=C4)Cl)Cl)/C#N
  • 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+
  • Key:SVENPFFEMUOOGK-SDNWHVSQSA-N

AGK2 is a drug which acts as a selective sirtuin 2 (SIRT2) inhibitor. It was one of the first selective SIRT2 inhibitors developed,[1] and inhibits SIRT2 with an IC50 of 3.5μM, making it less potent than other more recently developed compounds, but it is still widely used in research. It has good selectivity for SIRT2 over SIRT1 and SIRT3, though its activity at other subtypes is less well characterised. It has antiviral effects,[2][3] and has been used to study the potential role of SIRT2 inhibitors for the treatment of Parkinson’s disease as well cardiac fibrosis,[4] and some forms of cancer.[5][6][7][8]

References

  1. ^ Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, et al. (July 2007). "Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease". Science. 317 (5837): 516–519. Bibcode:2007Sci...317..516O. doi:10.1126/science.1143780. PMID 17588900.
  2. ^ Li Y, Bie J, Song C, Li Y, Zhang T, Li H, et al. (December 2023). "SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1". EMBO Reports. 24 (12) e57500. doi:10.15252/embr.202357500. PMID 37870259.
  3. ^ Kim J, Ha J, Song C, Sajjad MA, Kalsoom F, Kwon H, et al. (2025). "Sirtuin 2 inhibitor AGK2 exerts antiviral effects by inducing epigenetic suppression of hepatitis B virus covalently closed circular DNA through recruitment of repressive histone lysine methyltransferases and reduction of cccDNA". Frontiers in Cellular and Infection Microbiology. 15 1537929. doi:10.3389/fcimb.2025.1537929. PMC 12014779. PMID 40270769.
  4. ^ Akbulut M, Keskin Aktan A, Sonugür G, Özen Akarca S, Bahar AN, Kavak H, et al. (January 2025). "Protective Effects of SIRT2 Inhibition on Cardiac Fibrosis". Anatolian Journal of Cardiology. 29 (4): 173–180. doi:10.14744/AnatolJCardiol.2025.4770. PMC 11965944. PMID 39885712.
  5. ^ Mai A (April 2010). "Small-molecule chromatin-modifying agents: therapeutic applications". Epigenomics. 2 (2): 307–324. doi:10.2217/epi.10.7. PMID 22121876.
  6. ^ Villalba JM, Alcaín FJ (2012). "Sirtuin activators and inhibitors". BioFactors. 38 (5): 349–359. doi:10.1002/biof.1032. PMC 3467333. PMID 22730114.
  7. ^ Bai X, Yao L, Ma X, Xu X (2018). "Small Molecules as SIRT Modulators". Mini Reviews in Medicinal Chemistry. 18 (13): 1151–1157. doi:10.2174/1389557516666160620095103. PMID 27334466.
  8. ^ Gao Q, Yang L, Ye S, Mai M, Liu Y, Jiang X, et al. (July 2025). "Targeting SIRT2 induces MLH1 deficiency and boosts antitumor immunity in preclinical colorectal cancer models". Science Translational Medicine. 17 (807) eadv0766. doi:10.1126/scitranslmed.adv0766. PMID 40668890.
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