Table 1.
Small-molecule compounds targeting SIRT3 for cancer therapy.
| Name | Chemical Structure | Mechanism | Cancer cell type | EC50/ IC50 | Pharmacological interventions | Preclinical tumor model | Ref. |
|---|---|---|---|---|---|---|---|
| Diethyl 1-(3,4-dimethoxybenzoyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate |
|
Increased the activity of glutamate dehydrogenase (GDH), the level of deacetylating K68- and K122-acMnSOD and reduced hypoxia and EMT targey modulation | Triple-negative breast cancer (TNBC), MDA-MB-231, thyroid cancer, CAL-62 | / | MDA-MB-231 and CAL-62 are treated with 50 μM for 48 h. | / | 102 |
| Diethyl 1-(3,5-dimethoxybenzoyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate |
|
Increased the GDH activity, and reduced hypoxia and EMT targey modulation | TNBC, MDA-MB-231, thyroid cancer, CAL-62 | IC50 = 3.64 μM IC50 = 16.7μM |
MDA-MB-231 and CAL-62 are treated with 50 μM for 48 h. | / | 102 |
| ADTL-SA1215 | Increased deacetylating SKP, activate PINK1-Parkin pathway and reversed Warburg effect | TNBC, MDA-MB-231 | EC50 = 0.21 μM IC50 = 2.19 ± 0.16 μM |
MDA-MB-231 is treated with 5 μM for 24 h. In MDA-MB-231 TNBC xenograft model with 25 mg/kg for 16 days. | / | 103 | |
| MY-13 |
|
Regulated the SIRT3/Hsp90/AKT signaling pathway to induce autophagy-dependent cell death and apoptosis | Colorectal cancer, RKO, HCT116 | IC50 = 5.32 μM IC50 = 14.71 μM |
RKO is treated with 5.23 μM for 24 h. HCT116 is treated with 14.71μM for 24 h. In xenograft model with 40 and 50 mg/kg | Colorectal cancer | 113 |
| Honokiol |
|
Reduced Kla level on CCNE2 | Hepatocellular carcinoma, Huh7, TNBC, MDA-MB-231, | EC50 = 0.17 μM IC50 = 44.89 ± 1.86 μM |
Huh7 is treated with 10 μM for 24 h. HCC mice is treated with 10 mg/kg. | Lung cancer | 69 |
| Compound 31 |
|
Increased the activity of GDH and the level of deacetylating K68- and K122-acMnSOD | TNBC, MDA-MB-231 | / | MDA-MB-231 is treated with 50 μM for 24 h. | / | 101 |
| Resveratrol |
|
Inhibited SIRT3/AMPK/autophagy pathway | TNBC, MDA-MB-231 | EC50 = 55.19 μM IC50 = 98.84 ± 2.16 μM |
4T1 is treated with 25μM for 24 h. In MDA-MB-231 TNBC xenograft model with 40 mg/kg. | / | 114 |
| Melatonin |
|
Activated pyruvate dehydrogenase complex and reversed Warburg effect | Lung cancer, A549, LLC, PC9, | IC50 = 2.5 mM, IC50 = 1.2 mM IC50 = 2.8 mM |
PC9 and LCC is treated with 1.5 mM for 24 h. Lewis mouse model is treated with 10 mg/kg. | / | 115 |
| 3-triazolylpyridine |
|
/ | Leukemia, non-small cell lung cancer, colorectal cancer | IC50 = 16 nM | HeLa is treated with 4.7μM for 48 h. SK-MEL-28 is treated with 10 μM for 48 h. | Leukemia, ovarian, colon cancer | 31 |
| YC8-02 |
|
Increased mitochondrial protein acetylation and autophagy | Diffuse large B cell lymphomas | IC50 = 0.53 μM | DLBCL is treated with 10 μM for 24 h. C57BL/6 mice is treated with 30 mg/kg | / | 70 |
| JH-T4 |
|
Increased mitochondrial protein acetylation and autophagy | Diffuse large B cell lymphomas | IC50 = 2.5 μM | DLBCL is treated with 10 μM for 24 h. | / | 70 |
| Biotin-TM3 |
|
Increased mitochondrial protein acetylation and autophagy | Diffuse large B cell lymphomas | IC50 = 15 μM | DLBCL is treated with 10 μM for 24 h. | / | 70 |
| Compound 8a |
|
/ | / | IC50 = 51.6 ± 1.28 | / | / | 104 |
| Compound 15 |
|
/ | / | IC50 = 23.4 ± 2.11 | / | / | 104 |
| 4'-Bromo-resveratrol |
|
Induced apoptosis and a G0/G1 phase arrest through a metabolic reprogramming | Melanoma G361, SK-MEL-28, SK-MEL-2 |
IC50 = 143.0 ± 3.6 μM | G361, SK-MEL-28 and SK-MEL-2 are treated with 0.025 mM for 24 h. | / | 107 |
| Compound 15 |
|
/ | / | IC50 = 0.37 ± 0.05 μM | / | / | 108 |
| Butyrate |
|
Induce apoptosis through activating PDHA1 hyperacetylation and reversing the Warburg effect | Colorectal cancer, HCT116 |
/ | HeLa and HCT116 are treated with 5 mM for 24 h. | / | 116 |
| Compound P6 |
|
Induced a G0/G1 phase arrest | Mixed-lineage leukemias THP-1, MOLM-13, SEM and MV4-11 |
IC50 = 7.2 ± 0.5 μM | THP-1, MOLM-13, SEM and MV4-11 are treated with 0.9 μM for 24 h. | / | 105 |
| Compound P19 |
|
/ | Mixed-lineage leukemias | / | THP-1, MOLM-13, SEM and MV4-11 are treated with 0.9 μM for 24 h. | / | 105 |
| Compound 8b |
|
/ | Diffuse large B-cell lymphoma, colon, HCT116, breast MCF7, nonsmall cell lung carcinoma NCI-H460 | IC50 = 6 μM | NCI-H460 is treated with 1 μM for 24 h. | / | 106 |
| Kaempferol Apigenin |
|
/ | TNBC, T47D, MCF-7, MDA-MB-231, MDA-MB-468 | IC50 = 123 ± 0.4 μg/mL IC50 = 132 ± 0.23 μg/mL IC50 = 24.85 ± 0.12 μg/mL IC50 = 27.6 ± 1.34 μg/mL IC50 = 25.01 ± 0.11 μg/mL |
T47D, MCF-7, MDA-MB-231, MDA-MB-468 are treated with 20 μM for 24 h. | / | 109 |