Table 1.

Therapeutics under evaluation as potential disease-modifying osteoarthritis drugs that may target joint tissue senescence.

Drug Name	Target	Stage Of Trials	Reference
Senolytics
Dasatinib	BCR-ABL, SRC, c-KIT, ephrin A receptor	Mouse ACLT OA model Phase I clinical trial for IPF and CKD	28, 29 30, 31 NCT02874989 NCT02848131
Quercetin	PI3K and serpins	Mouse ACLT OA model Phase I clinical trial for IPF and CKD	28, 29 30, 31 NCT02874989 NCT02848131
UBX-0101	MDM2 and p53	Mouse ACLT OA model Phase 1 clinical OA trial Phase 2 clinical OA trial	12,20 NCT03513016 NCT04129944
Piperlongumine	Oxidation resistance protein OXR1	In vitro studies Studies of psoriasis In vitro studies of human OA chondrocytes	32, 33 34 35
Fisetin	PI3K, CDK6, IKK	In vitro human cells Mouse DMM OA model Phase 1 /2 clinical OA trial	36, 37 38 NCT04210986
Navitoclax, ABT-199, A1331852	BCL-2, BCL-X1, BCL-W	Mouse DMM OA model	42–44
Senomorphics
Ruxolitinib	JAK 1/2	In vitro inhibition of SASP	23
Rapamycin	mTOR	Mouse DMM OA model Guinea pig spontaneous OA	45, 48–49 50
Metformin	AMPK	In vitro increased autophagy Mouse DMM OA model Guinea pig spontaneous OA	51 52 50
XAV-939 and C113	Wnt	Mouse DMM model	55
SM04690	CLK2 and DYRK1A, Wnt pathway	Phase 2a clinical OA trial Phase 2b clinical OA trial Phase 3 clinical OA trial	NCT02536833 NCT03122860 NCT04385303
BMS-345541	IKK	Mouse DMM OA model	58
Cytokine inhibitors
IL-17 neutralizing antibody	IL-17	Mouse ACLT OA model	20
Lutikizumab	IL-1α/β	Phase 2 clinical OA trial	62 NCT02087904
Canakinumab	IL-1β	Phase 2 clinical OA trial	63 NCT04864392
Tocilizumab	IL-6	Phase 3 clinical OA trial	65 NCT02477059
Entanercept	TNF-α	Phase 2 clinical OA trial	66 NCT00394563