EX 527 is a potent and selective SIRT1 inhibitor with IC50 of 38 nM, exhibits >200-fold selectivity against SIRT2 and SIRT3.

YC8-02 is a small molecule mitochondrial-targeting SIRT3 inhibitor with IC50 of 0.53 uM.YC8-02 inhibits SIRT1 and SIRT2 with IC50 of 2.8 and 0.062 uM in in vitro biochemical assays.YC8-02 manifested increased ratio of mitochondria to total cell concentration, as measured by mass spectrometry in purified mitochondria extracts and total cell lysates.YC8-02 increased mitochondrial protein acetylation, inhibited GDH activity and induced autophagy in DLBCL cells.YC8-02 could phenocopy the effects of SIRT3 depletion.YC8-02 (30 mg/kg) caused regression of the tumors in DLBCL xenografts, with no evidence of discomfort or weight loss.

SIRT6 activator CL5D is a novel small-molecule activator of SIRT6 deacetylation, stimulates 4-fold activation of SIRT6 (1 uM) against H3K9ac (20 uM) at 3 uM.CL5D demonstrate competitive inhibition with Ki of 13.4 uM.CL5D exhibited time-dependent deacetylation at H3K9 by SIRT6 in HEK293T cells.

SIRT5 inhibitor 32 is an efficient, cellularly active small molecule that targets SIRT5.SIRT5 inhibitor 32 inhibits cell growth of SIRT5-dependent AML cell lines SKM-1, OCIAML2 and MOLM-13 with IC50 of 9, 20, and 24 uM, respectively.SIRT5 inhibitor 32 is also shown to inhibit SIRT5 in HeLa cells by using an assay that produce in-cell fluoresence in response to SIRT5 activity in the mitochondria.SIRT5 inhibitor 32 displays cytoselective toxicity towards SIRT5-dependent AML cells (SKM-1) over HEK293T cells in culture.

SIRT3 inhibitor 8 is a SIRT3 selective inhibitor with IC50 of 6 uM, 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2.SIRT3 inhibitor 8 reduced DLBCL cell viability and triggered activation of autophagy.

SIRT2 inhibitor 56 is a potent selective SIRT2 inhibitor with IC50 of 780 nM.SIRT2 inhibitor 56 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 56 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 56 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=9.1 uM).SIRT2 inhibitor 56 induces apoptosis and shows anti-proliferation effect in OCI-Ly8-LAM53 (OCI) cells.

SIRT2 inhibitor 55 is a potent and selective SIRT2 inhibitor with IC50 of 250 nM.SIRT2 inhibitor 55 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 55 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 55 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=11.9 uM).

NH4-6 is a potent, selective pan SIRT1-3 inhibitor with IC50 of 3.0/0.032/2.3 uM for SIRT1/2/3, respectively.NH4-6 does not inhibits SIRT5 and SIRT6.NH4-6 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

NH4-13 is a potent, SIRT2-selective inhibitor with IC50 of 87 nM, no inhibition against SIRT1/3/5/6 (CI50>50 uM).NH4-13 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

DK1-04 is a potent, selective, cell-permeable small-molecule SIRT5 inhibitor with IC50 of 0.34 uM, shows no inhibition on SIRT1-3/6 at 83 uM.

Sirt2-IN-5 is a potent SIRT2 inhibtor.

AGK7 is a potent inhibitor of sirtuin 2 (SIRT2). AGK7 rescues alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. AGK7 protects against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease.

SIRT1 activator 3 is a potent activator of Sirt1 and suppresses TNF-α in a dose-dependent manner. SIRT1 activator 3 has the potential for anti-obesity or anti-diabetic researches.

SIRT7 inhibitor 97491, a potent SIRT7 inhibitor with an IC50 of 325 nM, reduces deacetylase activity of SIRT7 in a dose-dependent manner. SIRT7 inhibitor 97491 prevents tumor progression by increasing p53 stability through acetylation at K373/382. SIRT7 inhibitor 97491 promotes apoptosis through caspase pathway..

Cambinol is a SIRT1 and SIRT2 inhibitor with IC50 values of 56 and 59 μM, respectively.

CAY10602 is a SIRT1 activator.

Inauhzin(INZ) is a novel small molecule that effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress(IC50=3 uM, in A549 cell).

JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC50 of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC50>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research.

Ainsliadimer C, a potential activator of SIRT1, ameliorates inflammatory responses in adipose tissue.

ADTL-SA1215 is a first-in-class specific small-molecule activator of SIRT3 that modulates autophagy in triple negative breast cancer.

NRD167 is a potent and selective SIRT5 inhibitor.

3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol, a SIRT1 activator, exhibits significant stimulation of SIRT1 activity. Anti-tumor activity.

7-Chloro-4-(piperazin-1-yl)quinolone is an important scaffold in medicinal chemistry. 7-Chloro-4-(piperazin-1-yl)quinolone is a potent sirtuin inhibitor and also inhibits the serotonin uptake (IC50 of 50 μM). 7-Chloro-4-(piperazin-1-yl)quinolone exhibits antimalarial activity on D10 and K1 strains of P. falciparum with IC50s of 1.18 μM and 0.97 μM, respectively.

SRT3657 is a brain-permeable activator of SIRT1, with neuroprotective effect.

CHIC35, an analog of EX-527, is a potent and selective inhibitor of SIRT1 (IC50=0.124 µM). CHIC35 shows potential selective inhibition against SIRT1 over SIRT2 (IC50=2.8 µM) or SIRT3 (IC50>100 µM). CHIC35 has anti-inflammatory effects and can be used for CHARGE syndrome research.

SIRT-IN-3 is a potent SIRT inhibitor, with an IC50 of 17 μM for SIRT1. SIRT-IN-3 shows about 4-fold and 14-fold selectivity for SIRT1 over SIRT2 and SIRT3, respectively (IC50 of 74 μM and 235 μM for SIRT2 and SIRT3, respectively).

Nicotinamide riboside malate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.

Nicotinamide riboside tartrate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside tartrate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside tartrate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.

MC3482 is a potent, specific SIRT5 inhibitor, increases the ammonia content in cells leading to autophagy and mitophagy, shows selective SIRT5 inhibition vs SIRT1-3.

SRTCX1003 (SRTCX-1003) is a small molecule activator of SIRT1 (STAC) with EC1.5 of 0.61 uM, enhances deacetylation of cellular p65 protein with IC50 of 1.42 uM in cellular p65 acetylation assay.