FLS-359 (FLS359) is a selective, allosteric inhibitor of sirtuin 2 (SIRT2) deacetylase activity with IC50 of 3 uM, shows no activity against SIRT1 and SIRT3, exhibits broad-spectrum antiviral activity.
FLS-359 is not competitive with NAD+, FLS-359 is substrate selective, inhibiting deacetylation but not demyristoylation.
FLS-359 induces degradation of c-Myc protein in MDA-MB-231 breast adenocarcinoma cells.
FLS-359 binds selectively to SIRT2 and induces an allosteric rearrangement of the active site, reducing the rate of deacetylation.
FLS-359 shows activity against multiple RNA and DNA viruses in cultured cells (SARS-CoV-2/human Calu3, IC50=0.3 uM; HCMV/human MRC-5, IC50=0.5 uM).
FLS-359 markedly reduces EBV lytic activation in Akata cells, inhibitsthe accumulation of viral immediate-early (BZLF1), early (BMRF1), and late (BLLF1) mRNAs.
FLS-359 inhibits HCMV spread in diploid fibroblasts, inhibits the accumulation of intracellular HCMV RNAs and DNA and reduces the infectivity of virus progeny.
FLS-359 (50 mg/kg, p.o., b.i.d.) inhibits HCMV infection in humanized models of HCMV infection.