(R)-ND-336 is a highly potent and selective MMP-9 inhibitor, displaying a K i value of 19 nM. It also exhibits inhibitory activity against MMP-2 (K i = 127 nM) and MMP-14 (K i =119 nM). With its significant potential, (R)-ND-336 is being investigated in the field of diabetic foot ulcers (DFUs) research [1].

(R)-ND-336 poorly inhibits other MMPs (K i >100 μM). (R)-ND-336 has a long residence time (the time the inhibitor is bound to MMP-9, calculated as 1/k off ) of 300 min [1]. A favorable IC50value of 143 μM afforded a therapeutic index (IC 50 /K i for MMP-9) ratio of 7530, indicating that (R)-ND-336 is not cytotoxic [1].

(R)-ND-336 (50 μg/wound/day for 14 days) accelerates wound healing faster [1]. (R)-ND-336 has an AUC of 1.3 μM min after topical administration and 35 μM min following intravenous dosing, for an AUC top /AUC iv ratio of 3.7%, indicating minimal absorption after topical administration in db/db mice [1]. Animal Model: Female db/db mice (BKS.Cg-Dock7 m+/+ Lepr db /J, 8-weeks old, ～40 g body weight) [1] Dosage: 50 μg Administration: Wound; once a day for 14 days Result: Accelerated wound healing faster and showed complete inhibition of MMP-9.