Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Table 2 The development of synthetic ADAMTS aggrecanase inhibitors

Compound	Target selectivity
Engineered N-TIMP-3 [82]	ADAMTS4, ADAMTS5
(2R)-N⁴-hydroxy-2-(3-hydroxybenzyl)-N¹-[(1S,2R)-2-hydroxy-,3-dihydro-1H-inden-1-yl] butanediamides [83]	ADAMTS4, ADAMTS5
N-hydroxyformamides [85]	ADAMTS4, ADAMTS5
1,2,4-triazole-3-thiol scaffolds [86]	ADAMTS5 > ADAMTS4
N-((8-Hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamides [87]	ADAMTS5 > ADAMTS4,
5-((1H-Pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one [88]	ADAMTS5 > ADAMTS4
4-(benzamido)-4-(1,3,4-oxadiazol-2-yl) butanoic acid [89]	ADAMTS4, ADAMTS5
1-sulfonylaminocyclopropanecarboxylates, N-substituted sulfonylamino-alkanecarboxylates [90]	ADAMTS5
1,3,5-triazine core [91]	ADAMTS5
CRB017 (antibody against ancillary domain) [92]	ADAMTS5
AGG-523 (Pfizer Inc.)	ADAMTS4, ADAMTS5

Engineered and synthetic compounds are being developed to obtain selectivity toward the inhibition of the aggrecanases ADAMTS4 and ADAMTS5 to prevent cartilage destruction in both rheumatoid arthritis and osteoarthritis. ADAMTS, A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats; TIMP, tissue inhibitor of metalloproteinase.

ISSN: 1478-6362