(R)-ND-336

(R)-ND-336 is a potent and selective MMP-9 inhibitor with a Ki of 19 nM. (R)-ND-336 inhibits MMP-2 (Ki=127 nM) and MMP-14 (Ki=119 nM). (R)-ND-336 has the potential for diabetic foot ulcers (DFUs) research[1].

Research Areas >> Metabolic Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

MMP-9:19 nM (Ki)

MMP-2:127 nM (Ki)

MMP-14:119 nM (Ki)

(R)-ND-336 poorly inhibits other MMPs (Ki>100 μM). (R)-ND-336 has a long residence time (the time the inhibitor is bound to MMP-9, calculated as 1/koff) of 300 min[1]. A favorable IC50value of 143 μM afforded a therapeutic index (IC50/Ki 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 AUCtop/AUCiv ratio of 3.7%, indicating minimal absorption after topical administration in db/db mice[1]. Animal Model: Female db/db mice (BKS.Cg-Dock7m+/+Leprdb/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.

[1]. Trung T Nguyen, et al. Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing. J Med Chem. 2018 Oct 11;61(19):8825-8837.