TABLE 2.

Anti‐senescence and anti‐SASP strategies: target proteins, agents and clinical development status

Candidate senotherapy	Target class/target	Agent	Class	Development status
				In vitro inducer	Preclinical models	Clinical trials
Senolytics	Pan‐kinase	Quercetin	Small inhibitor	Replicative Senescence		Phase II Chronic Kidney Disease NCT02848131
	Pan‐receptor tyrosine kinase	Dasatinib	Small inhibitor	Replicative Senescence		Phase II Skeletal Health in aging NCT04313634
	Pro‐survival proteins BCL‐2, BCL‐XL, BCL‐W	ABT‐737	Small inhibitor	Replicative Senescence Oncogene Induced Senescence Irradiation, Cytostatic drugs
		A1155463	Small inhibitor
		A‐1331852	Small inhibitor
		ABT‐263 (Navitoclax)	Small inhibitor
	MDM2/p53 protein interaction	UBX0101	Small inhibitor	Replicative Senescence	Osteoarthritis mouse model	Phase II Knee Osteoarthritis NCT04129944
		P5091, P22077	USP7 inhibitor	Replicative Senescence Irradiation, Cytostatic drugs	Doxorubicin‐treated mice
	FOXO4	FOXO4 peptide	Peptide blocking interaction with p53	Replicative Senescence Irradiation, Cytostatic drugs	XpdTTD/TTD mice, p16‐3MR aged mice
	HSP90	Alvespimycine (17‐DMAG)	Small inhibitor, antibiotic	Replicative Senescence Irradiation, Oxidative stress	Ercc1 ‐/∆ progeroid mice
		Ganetespib	Small inhibitor
	Unknown	Fisetin	Flavonoid polyphenol	Replicative Senescence	Ercc1 ‐/∆ progeroid and old INK‐ATTAC mice	Phase II Frail Elderly Syndrome NCT03675724, NCT03430037
		Luteolin	Flavonoid polyphenol	Replicative Senescence		Phase I/II Osteoarthritis NCT04210986
						Phase II Chronic Kidney Diseases, Diabetes NCT03325322
						Phase II Skeletal Health in aging NCT04313634
	Na+/K+ ATPase	Ouabain	Cardiac Glycosides	Replicative Senescence Irradiation, Cytostatic drugs.	Lung adenocarcinoma, melanoma xenograft
					Liver cancer, ACP mouse models
		Digoxin			Irradiated mice
					Ageing mice
	Mitochondria	MitoTam	Mitochondria‐targeted tamoxifen	Replicative Senescence, Cytostatic drugs	Ageing mice
Vectorisation	Encapsulation of drugs with galacto‐oligosaccharides	Mesoporous Silica Nanoparticles		Oncogene Induced Senescence, Cytostatic drugs	Melanoma xenograft
		Multiple cargo: doxorubicin, navitoclax,			Triple negative breast cancer xenograft
					Fibrotic lungs mouse model
	Galactose‐modified prodrug	Duocarmycin derivatives		Replicative Senescence, Oncogene Induced Senescence Irradiation Cytostatic drugs	ACP mouse model
					Irradiated mice
		Navitoclax		Oncogene Induced Senescence Irradiation, Cytostatic drugs	NSCLC mouse models
SASP prouction modulators	IKK, NF‐κB and DICER	Metformin	Small inhibitor	Replicative Senescence, Oncogene Induced Senescence		Approved for Diabetes
	mTOR	Rapamycin	Small inhibitor	Replicative Senescence, Irradiation, Cytostatic drugs	Ageing mice	Approved immunosuppressor
	JAK‐STAT	Ruxolitinib	Small inhibitor	Replicative Senescence	Ageing mice	Approved immunosuppressor
	Glucocorticoids Receptor	Corticosterone, Cortisol	Glucocorticoids	Irradiation		Approved immunosuppressor
	p38MAPK		Small inhibitor
SASP blocking antibodies	IL1A, IL1B, IL1Receptor	Rilonacept, Canakinumab, Anakinra				Clinicaly approved immunosuppressors
	TNF	Etanercept, Infliximab
	IL6, IL6R	Siltuximab, Tocilizumab
Immunotherapies	Antibody‐dependent cell‐mediated cytotoxicity with NK cells	DPP4 antibody	Antibody	Replicative Senescence
	NKG2D CAR‐T cells
Calories restriction mimetics		2‐deoxy‐D‐glucose	Glucose analogue	Replicative Senescence Oncogene Induced Senescence
		Resveratrol	Polyphenol	Replicative Senescence Oncogene Induced Senescence	Ageing mice