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

MMP9:19 nM (Ki), MMP14:119 nM (Ki), MMP2:127 nM (Ki)

(R)-ND-336 exhibits minimal inhibition of other MMPs, with an inhibition constant (K i ) greater than 100 μM. It possesses a prolonged residence time of 300 minutes, indicative of the duration it remains bound to MMP-9. Moreover, (R)-ND-336 demonstrates a promising IC50 value of 143 μM, resulting in a therapeutic index ratio of 7530. This highlights its significant selectivity for MMP-9 over other MMPs without being cytotoxic [1].

(R)-ND-336, applied topically at 50 μg per wound daily over a 14-day period, significantly enhances wound healing, as evidenced by accelerated healing rates. Pharmacokinetic measurements reveal that (R)-ND-336 achieves an area under the curve (AUC) of 1.3 μM·min following topical administration and 35 μM·min after intravenous administration, with a resultant AUC ratio (topical to intravenous) of 3.7%. This indicates that topical application results in minimal systemic absorption in the db/db mouse model. Specifically, the study utilized female db/db mice, aged 8 weeks and weighing approximately 40g, to assess the compound's efficacy. The findings demonstrate not only accelerated wound healing but also the complete inhibition of MMP-9 enzyme activity, thus proving (R)-ND-336's potential therapeutic benefits.