Table 1.
Senolytic agents and their molecular targets
| Senolytic agents | Target | Effective type of senescent cells | Effective for aging mouse model | Effective for CVD mouse model | Ongoing clinical trials | Reference | |
| 1 | Dasatinib | Dependence receptor/Src kinase/Tyrosine kinase | Irradiated human preadipocytes, human lung fibroblasts (IMR-90), MEFs, mouse preadipocytes (adipose-derived stem cells) | Yes [irradiation, progeria (Ercc1−/Δ), chronological aging] | Yes [atherosclerosis (ApoE−/−)] | (D + Q); chronic kidney disease, idiopathic pulmonary fibrosis, hematopoietic stem cell transplantation | (105, 107, 125–129) |
| 2 | Quercetin | Bcl-2 family, p53/p21/serpine, PI3K/AKT signaling | Irradiated HUVECs, human lung fibroblasts (IMR-90), mouse bone marrow-derived stem cells, MEFs | Yes [irradiation, progeria (Ercc1−/Δ), chronological aging] | Yes [atherosclerosis (ApoE−/−)] | (D + Q); chronic kidney disease, idiopathic pulmonary fibrosis, hematopoietic stem cell transplantation | (105, 107, 125–129) |
| 3 | Navitoclax (ABT-263) | Bcl-2 family (Bcl-2, Bcl-xl, and Bcl-w) | Human lung fibroblasts (IMR-90, WI-37; irradiated, RAS induction, replicative), irradiated human renal epithelial cells, MEFs | Yes (irradiation, chronological aging) | N/A | N/A | (34, 126) |
| 4 | TW-37 | Bcl-2 family (Bcl-2, Bcl-xl, and Mcl-1) | MEFs passaged in high oxygen condition (20%) | N/A | N/A | N/A | (126) |
| 5 | ABT-737 | Bcl-W and Bcl-XL | Human lung fibroblasts (IMR-90) | Yes (irradiation) | N/A | N/A | (125) |
| 6 | Fisetin | PI3K/AKT signaling | Irradiated HUVECs | N/A | N/A | N/A | (130) |
| 7 | A1331852 | Bcl-2 family (Bcl-XL) | Irradiated human lung fibroblasts (IMR-90), HUVECs | N/A | N/A | N/A | (130) |
| 8 | A1155463 | Bcl-2 family (Bcl-XL) | Irradiated human lung fibroblasts (IMR-90), HUVECs | N/A | N/A | N/A | (130) |
| 9 | Foxo4-DRI | Foxo4-p53 interaction | Irradiated human lung fibroblasts (IMR-90, WI-38), foreskin fibroblasts (BJ cells) | Yes [doxorubicin, progeria (XpdTTD/TTD), chronological aging] | N/A | N/A | (106) |
| 10 | Alvespimycin (17-DMAG) | HSP90 | Ercc1−/− MEFs | Yes [progeria (Ercc1−/Δ)] | N/A | N/A | (131) |
| 11 | Tanespimycin (17-AAG) | HSP90 | Ercc1−/− MEFs | N/A | N/A | N/A | (131) |
| 12 | Geldanamycin | HSP90 | Ercc1−/− MEFs | N/A | N/A | N/A | (131) |
| 13 | Piperlongumine | p53/p21 & Bcl-2 family (PUMA) | Irradiated human lung fibroblasts (WI-38) | N/A | N/A | N/A | (132) |
| 14 | Panobinostat | Histone deacetylase | Chemotherapy-induced senescent NSCLC and HNSCC cells | N/A | N/A | N/A | (133) |
MEF: mouse embryonic fibroblast, HUVEC: human umbilical vein endothelial cell, NSCLC: non-small cell lung carcinoma, HNSCC: head and neck squamous cell carcinoma, D + Q: combination of dasatinib and quercetin, CVD: cardiovascular disorder, N/A: not applicable.