FLS-359

FLS-359
Clinical data
Drug class	Sirtuin 2 (SIRT2) inhibitor
Identifiers
	IUPAC name 2-[7-(2,4-dimethylimidazol-1-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-[(4-pyrazol-1-ylphenyl)methyl]-1,3-thiazole;
CAS Number	2309398-79-4;
PubChem CID	138571253;
ChemSpider	129601602;
ChEMBL	ChEMBL6065272;
Chemical and physical data
Formula	C27H26N6S
Molar mass	466.61 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CN(C(=N1)C)C2=CC3=C(CCN(C3)C4=NC=C(S4)CC5=CC=C(C=C5)N6C=CC=N6)C=C2;
	InChI InChI=1S/C27H26N6S/c1-19-17-32(20(2)30-19)25-9-6-22-10-13-31(18-23(22)15-25)27-28-16-26(34-27)14-21-4-7-24(8-5-21)33-12-3-11-29-33/h3-9,11-12,15-17H,10,13-14,18H2,1-2H3; Key:JRPPFSVORXBCPF-UHFFFAOYSA-N;

FLS-359 is a drug which acts as a selective allosteric inhibitor of the enzyme sirtuin 2 (SIRT2). It has moderate potency, inhibiting SIRT2 with an IC₅₀ of 3 μM, and shows broad-spectrum antiviral effects against both RNA and DNA viruses including hepatitis B and cytomegalovirus.^[1]^[2]^[3]

References

^ Roche KL, Remiszewski S, Todd MJ, Kulp JL, Tang L, Welsh AV, et al. (June 2023). "An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity". The Journal of Clinical Investigation. 133 (12) e158978. doi:10.1172/JCI158978. PMC 10266789. PMID 37317966.
^ Tang L, Remiszewski S, Snedeker A, Chiang LW, Shenk T (June 2024). "An allosteric inhibitor of sirtuin 2 blocks hepatitis B virus covalently closed circular DNA establishment and its transcriptional activity". Antiviral Research. 226 105888. doi:10.1016/j.antiviral.2024.105888. PMC 12053749. PMID 38641024.
^ Carter MF, Knight K, Kayode Y, Murphy EA (September 2025). "Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling". Antiviral Research. 241 106237. doi:10.1016/j.antiviral.2025.106237. PMID 40653174.

[1] Roche KL, Remiszewski S, Todd MJ, Kulp JL, Tang L, Welsh AV, et al. (June 2023). "An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity". The Journal of Clinical Investigation. 133 (12) e158978. doi:10.1172/JCI158978. PMC 10266789. PMID 37317966.

[2] Tang L, Remiszewski S, Snedeker A, Chiang LW, Shenk T (June 2024). "An allosteric inhibitor of sirtuin 2 blocks hepatitis B virus covalently closed circular DNA establishment and its transcriptional activity". Antiviral Research. 226 105888. doi:10.1016/j.antiviral.2024.105888. PMC 12053749. PMID 38641024.

[3] Carter MF, Knight K, Kayode Y, Murphy EA (September 2025). "Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling". Antiviral Research. 241 106237. doi:10.1016/j.antiviral.2025.106237. PMID 40653174.

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