Table 3.
Major compounds for eliminating senescent cells
| Compounds | Molecular targets | Animal models | Treatments | Outcomes | Clinical trials |
|---|---|---|---|---|---|
| ABT263 (Navitoclax) | BCL-2, BCL-XL (Chang et al., 2016; Zhu et al., 2016) | HFD-fed Ldlr−/− mice (Childs et al., 2016); 24-month old male C57BL/6 mice (Anderson et al., 2019). | 100 mg/kg ABT263 in PBS with 15% DMSO/7% Tween-20 (Childs et al., 2016); Oral gavage (50 mg/kg BW/day) for 7 days per cycle for 2 cycles with a 1-week interval between cycles (Anderson et al., 2019) | Inhibits atherogenesis onset and stabilizes atherosclerotic plaques (Childs et al., 2016); rejuvenates aged hematopoietic stem cells in mice (Chang et al., 2016); promotes cardiomyocyte regeneration (Anderson et al., 2019) | NCT00406809 (for relapsed or refractory lymphoid malignancies); NCT00445198 (for SCLC or other non-hematological malignancies |
| ABT737 | BCL-W, BCL-XL (Yosef et al., 2016) | 8 Gy-irradiated male mice; p14ARF-expressing mice | i.p. injection with 75 mg/kg for 2–4 days | Elimination of senescent cells in lungs and from the epidermis (Yosef et al., 2016) | N/A |
| Dasatinib (D) + Quercetin (Q) | Tyrosine protein kinases (Guo et al., 2018) | Aged and ApoE−/− mice (Roos et al., 2016); senescent cell-transplanted mice or aged (20–27-month old, 27.7 ± 2.7 months) mice. | Oral gavage (D, 5 mg/kg + Q, 10 or 50 mg/kg) single dose (Zhu et al., 2015), once monthly for 3 months or once weekly for 2 months) (Roos et al., 2016); D (5 mg/kg) + Q (50 mg/kg) (Xu et al., 2018); D (5 mg/kg) + Q (50 mg/kg) 3 consecutive days every 2 weeks for 2 months (Lewis-McDougall et al., 2019) | Improves systolic cardiac function and vascular relaxation (Zhu et al., 2015); decreases aortic calcification (Roos et al., 2016); alleviates physical dysfunction (Xu et al., 2018); activates resident CPCs (Lewis-McDougall et al., 2019) | NCT02874989 (for idiopathic pulmonary fibrosis) (Justice et al., 2019); NCT02848131, phase 2 (for chronic kidney disease; improve function of ADMSC) (Hickson et al., 2019) |
| 17-DMAG | HSP90 | Ercc1−/Δ mice (Fuhrmann-Stroissnigg et al., 2017); STZ-treated ApoE−/− mice (Lazaro et al., 2015) | 3x weekly with 1 week on followed by 2 weeks off, at 10 mg/kg by oral gavage beginning at 6 weeks of age (Fuhrmann-Stroissnigg et al., 2017); 2–4 mg/kg i.p., every other day for 10 weeks (Lazaro et al., 2015) | Extends health span (Fuhrmann-Stroissnigg et al., 2017), decrease atherosclerotic lesions and induces a more stable plaque phenotype (Lazaro et al., 2015) | NCT00088868 (for solid tumor or lymphoma) |
| Cardiac glycosides | ATP1A1 of Na+/K+ ATPase | Aged (24-month-old) or ApoE−/− mice (Shi et al., 2016) | Digoxin (2 mg/kg, i.p., twice weekly) (Triana-Martinez et al., 2019); Ouabain (1 mg/kg, i.p.) (Guerrero et al., 2019) | Reduce lung fibrosis, inhibits atherogenesis (Shi et al., 2016); tumor suppression (Guerrero et al., 2019) | Cardiac disease treatment, cancer therapy |
| FoxO4-DRI peptide | FoxO4-p53 interaction (Baar et al., 2017) | Doxorubicin-treated, fast- ageing XpdTTD/TTD, and naturally aged mice. | Injection at 5 mg/kg every other day for 2 weeks. | Induces the apoptosis of senescent cells, neutralizes doxorubicin-induced chemotoxicity, improves fitness, fur growth, and renal function in both fast ageing XpdTTD/TTD and naturally aged mice. | N/A (Cleara Biotech in UMC Utrecht is optimizing the drugs). |
17-DMAG, 17-dimethylaminoethylamino-17-demethoxygeldanamycin; ADMSC, adipose-derived mesenchymal stem cells; BCL-W, B cell lymphoma W; BCL-XL, B cell lymphoma extra large; DRI, D-retro inverso; i.p., intraperitoneal; N/A, not available; STZ, streptozotocin. For definitions of other abbreviations, please see the main text.