ND-336 / University of Notre Dame - LARVOL DELTA

Targeting Matrix Metalloproteinase-9 for Therapeutic Intervention in Diabetic Foot Ulcers. (PubMed, ACS Pharmacol Transl Sci) - "(R)-ND-336 showed better efficacy than becaplermin in diabetic mice. Becaplermin (PDGF) and HBO therapy work by decreasing MMP-9, but they do not completely suppress MMP-9 activity."

Journal • Review • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • MMP9

Collagen/chitosan/genipin hydrogel loaded with phycocyanin nanoparticles and ND-336 for diabetic wound healing. (PubMed, Int J Biol Macromol) - "Notably, Gel 2, with a weight ratio of collagen and chitosan at 25:75, was found to have an excellent capability to facilitate cell migration and in vivo studies further proved that Gel 2 nanocomposite hydrogel had the best ability to improve diabetic wound healing by promoting cell migration and decreasing MMP-9 expression. The collagen/chitosan/genipin hydrogel loaded phycocyanin and ND-336 can be harnessed for non-toxic and efficient treatment of wound healing management of diabetes."

Journal • Diabetes • Metabolic Disorders • MMP9

Network pharmacology reveals the potential of Dolastatin 16 as a diabetic wound healing agent. (PubMed, In Silico Pharmacol) - "In the docking study, a native ligand (a hydroxamate inhibitor) and (R)-ND-336 were employed as ligand controls, demonstrating binding energy values of - 6.6 and - 8.9 kcal/mol, respectively...Dolastatin 16 has the potential to act as an MMP9 inhibitor, offering promise for accelerating the wound healing process in diabetic foot conditions. The online version contains supplementary material available at 10.1007/s40203-023-00161-5."

Journal • Diabetes • Diabetic Neuropathy • Pain • MMP9

Targeting extracellular matrix remodeling sensitizes glioblastoma to ionizing radiation. (PubMed, Neurooncol Adv) - "Disruption of MT1-MMP sensitizes cells to radiation and can counteract invasion. (R)-ND336, which efficiently penetrates the brain, is therefore a novel radio-sensitizer in GBM."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • MMP14 • MMP2

Matrix Metalloproteinase-14 as an Instigator of Fibrosis in Human Pterygium and Its Pharmacological Intervention. (PubMed, ACS Pharmacol Transl Sci) - "(R)-ND-336 attenuated human conjunctiva fibroblast migration and mitigated collagen contraction, both activities required for the formation of pterygium. (R)-ND-336 holds the promise of a therapeutic recourse for pterygium as an orphan disease."

Journal • Corneal Abrasion • Eye Cancer • Fibrosis • Immunology • Ocular Melanoma • Oncology • Ophthalmology • ADAM10 • ADAM17 • ADAM9 • MMP14

Proteomics Identification of Targets for Intervention in Pressure Ulcers. (PubMed, ACS Chem Biol) - "In a mouse model of PUs, a highly selective inhibitor for MMP-9 and MMP-14, (R)-ND-336, accelerated wound closure in parallel with significant amelioration of ulcer stage. (R)-ND-336 holds promise as a first-in-class treatment for PUs."

Journal • MMP1 • MMP14 • MMP9

Metabolism of the Selective Matrix Metalloproteinase-9 Inhibitor (R)-ND-336. (PubMed, ACS Pharmacol Transl Sci) - "All three metabolites are poorer MMP-9 inhibitors, compared to (R)-ND-336 (MMP-9, K = 19 nM): M3, MMP-9 IC > 100 μM; M2, K = 390 nM; and M1, IC > 100 μM). The rat and the minipig were selected as the rodent and nonrodent species, respectively, for toxicology studies."

Journal • MMP9

Selective MMP-9 Inhibitor (R)-ND-336 Alone or in Combination with Linezolid Accelerates Wound Healing in Infected Diabetic Mice. (PubMed, ACS Pharmacol Transl Sci) - "We evaluated the efficacy of the selective small-molecule MMP-9 inhibitor, (R)-ND-336, in the infected diabetic mouse model of wound healing and showed that (R)-ND-336 alone or in combination with the antibiotic linezolid improves wound healing by inhibiting the detrimental MMP-9, mitigating macrophage infiltration to diminish inflammation, and increasing angiogenesis to restore the normal wound healing process. An advantage of this strategy is the ability to administer (R)-ND-336 concurrently with an antibiotic."

Combination therapy • Journal • Diabetes • Immunology • Inflammation • Metabolic Disorders • MMP9

Strategy for Treatment of Infected Diabetic Foot Ulcers. (PubMed, Acc Chem Res) - "(R)-ND-336 accelerated wound healing in diabetic mice by decreasing ROS and NF-κB, lowering inflammation, and increasing angiogenesis. (R)-ND-336 in combination with the antibiotic linezolid improved wound healing in infected diabetic mice by inhibiting MMP-9, which mitigated macrophage infiltration and increased angiogenesis, thereby restoring the normal wound healing process."

Journal • Diabetes • Immunology • Inflammation • Metabolic Disorders • Oncology • MMP9

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. (PubMed, J Med Chem) - "Furthermore, we synthesize and evaluate enantiomerically pure (R)- and (S)-ND-336, as inhibitors of the detrimental MMP-9, and show that the ( R)-enantiomer has superior efficacy in wound healing over becaplermin. Our results reveal that the mechanisms of pathology and repair are similar in diabetic mice and diabetic humans, and that ( R)-ND-336 holds promise for the treatment of DFUs as a first-in-class therapeutic."

Journal