TABLE 1.

Libraries screened for senolytic activity and identified classes of senolytics.

Senolytic class	Active compound(s)	Compound library tested to identify senolytic(s)	Cell model(s) used to identify activity	Ref.
Kinase inhibitors	Dasatinib	46 manually selected compounds known to target anti‐apoptotic pathways	HUVECs and preadipocytes induced by ionizing radiation	Zhu et al. (2015)
	Nintedanib, R406	Selleck Chem Kinase Inhibitor Library L1200 (n = 355)	HDFs induced by replicative exhaustion	Cho et al. (2020)
	Terreic acid a , PD‐98059 a , daidzein a , Y‐27632 a	SCREEN‐WELL® Kinase Inhibitor Library (n = 80)	HUVECs induced by oxidative stress, camptothecin treatment, and replicative exhaustion	Kusumoto et al. (2021)
Naturally occurring polyphenols	Quercetin	46 manually selected compounds known to target anti‐apoptotic pathways	HUVECs and preadipocytes induced by ionizing radiation	Zhu et al. (2015)
	Piperlongumine and analogs BRD4809, PL‐DI, PL‐7 and PL‐FPh	Manually selected compounds with bioactivities related to senescent cell viability	WI‐38 fibroblasts induced by ionizing radiation	Wang et al. (2016)
	Fisetin	Candidate study/10 flavonoid polyphenols	HUVECs induced by ionizing radiation, Ercc1 −/− MEFs induced by oxidative stress, IMR‐90 fibroblasts induced by etoposide treatment	Yousefzadeh et al. (2018); Zhu et al. (2017)
	Curcumin	10 flavonoid polyphenols	Ercc1 −/− MEFs induced by oxidative stress	Yousefzadeh et al. (2018)
	Curcumin analogs EF24, HO‐3867 and 2‐HBA	Candidate study also tested curcumin analog DIMC	WI‐38 fibroblasts induced by ionizing radiation	Li et al. (2019)
	o‐vanillin	Candidate study	naturally occurring senescent degenerated nucleus pulposus cells	Cherif et al. (2019)
	Procyanidin C1	46 natural compounds and plant extracts with putative anti‐aging properties	PSC27 prostate stromal cells induced by bleomycin treatment, replicative exhaustion, and oncogenic H‐RAS expression	Xu et al. (2021)
	Gingerenone A	4 plant extracts with anti‐inflammatory properties: Cat's claw, Devil's claw, Canadian goldenrod, and ginger	WI‐38 fibroblasts induced by ionizing radiation	Moaddel et al. (2022)
	Solidago virgaurea subsp. alpestris	Candidate study	HDFs induced by oxidative stress (senolysis observed after a chronic treatment period of 39 days)	Lammermann et al. (2018)
	Isatis tinctoria extract (active components not analyzed)	Six plant extracts with anti‐inflammatory properties: Isatis tinctoria, Rosmarinus officinalis, Rosa, Prunus persica, Nelumbo nucifera, Citrus unshiu Marcov	HDFs induced by replicative exhaustion	Kim et al. (2022)
BCL‐2 family inhibitors	ABT‐263	37 manually selected compounds with bioactivities related to senescent cell viability	WI‐38 fibroblasts induced by ionizing radiation	Chang et al. (2016)
	A1331852, A1155463	Candidate study	HUVECs and IMR‐90 fibroblasts induced by ionizing radiation	Zhu et al. (2017)
	ABT‐737	Candidate study	IMR‐90 fibroblasts induced by exhaustive replication, etoposide treatment and oncogenic H‐Ras expression	Yosef et al. (2016)
	S63845, UM177, AZD5991	Candidate study	PC3 and LNCaP prostate tumor cells induced by treatment with docetaxel and palbociclib	Troiani et al. (2022)
Heat shock protein inhibitors	17‐DMAG and other HSP90 inhibitors	SCREEN‐WELL® autophagy library (n = 97)	Ercc1 −/− MEFs induced by oxidative stress	Fuhrmann‐Stroissnigg et al. (2017)
	25‐hydroxycholesterol	Candidate study, also tested NCI‐41356	Fibro‐adipogenic progenitors, satellite cells, and skeletal muscle myoblasts induced by doxorubicin treatment	Limbad et al. (2022)
BET family protein degraders	ARV825, I‐BET151, I‐BET762, JQ1, OTX015, PFI‐1	TAKEDA drug discovery library (n = 47,000)	IMR‐90 fibroblasts induced by oncogenic H‐Ras expression	Wakita et al. (2020)
	JQ1	Candidate study	HDFs induced via bleomycin treatment	Go et al. (2021)
P53 stabilizers	RG‐7112	Candidate study	Naturally occurring senescent annulus fibrosus and nucleus pulposus cells	Cherif et al. (2020)
	USP7 inhibitors P5091 and P22077	Candidate study	WI‐38 fibroblasts induced by ionizing radiation and exhaustive replication	He, Li, et al. (2020)
Other repurposed anti‐cancer drugs	GL‐V9	Candidate study	Naturally occurring senescent MDA‐MB‐231 breast cancer cells and MEFs induced by exhaustive replication	Yang, Tian, et al. (2021)
	Panobinostat	Candidate study	A549 lung carcinoma cells induced by paclitaxel and cisplatin treatment	Samaraweera et al. (2017)
	MitoTam	Candidate study	4 T1 and MCF7 breast cancer cells induced by doxorubicin treatment, RPE‐1 and HFP‐1 cells induced by BrdU treatment, and BJ fibroblasts induced by exhaustive replication	Hubackova et al. (2019)
Cardiac steroids	Bufalin, cinobufagin, convallatoxin, digoxin, digitoxin, ouabain, peruvocide, proscillaridin A	LOPAC and Prestwick libraries of pharmacologically active compounds, GreenPharma and SCREEN‐WELL® natural compound libraries, and one library of venoms and venom‐derived peptides (n = 3742)	IMR‐90 fibroblasts induced by oncogenic H‐Ras expression and etoposide treatment, A549 lung adenocarcinoma cells induced by bleomycin treatment, and SK‐MEL‐103 melanoma cells induced by palbociclib treatment	Guerrero et al. (2019); Triana‐Martinez et al. (2019)
PPRα agonists	Fenofibrate	Prestwick library of pharmacologically active approved compounds (n = 1120)	T/C‐28a2 chondrocytes induced by treatment with IL‐6	Nogueira‐Recalde et al. (2019)
Antibiotics	Azithromycin, roxithromycin	15 manually selected approved drugs	MRC‐5 and BJ fibroblasts induced by treatment with BrdU	Ozsvari et al. (2018)
	Nigericin	Candidate study	Endometrial and Warton jelly‐derived MSCs induced by oxidative stress, endometrial MSCs induced by exhaustive replication, dental pulp MSCs induced by doxorubicin treatment, A459 lung adenocarcinoma cells induced by etoposide treatment	Deryabin et al. (2022)

Abbreviations: HDF, human dermal fibroblast; HUVEC, human umbilical vein endothelial cell; MEF, murine embryonic fibroblast; MSC, mesenchymal stem cell.

^a Senotherapeutic activity identified but not tested specifically for senolytic activity.