MMP408

MMP408 is an inhibitor of matrix metalloproteinase-12 (MMP-12; IC₅₀ = 2 nM).¹ It is selective for MMP-12 over MMP-3, -9, -13, and -14 (IC₅₀s = 351, 1,300, 120, and 1,100 nM, respectively) and MMP-1, MMP-7, and disintegrin and metalloproteinase domain-containing protein 17 (ADAM17/TACE; IC₅₀s = >6, >22, and >25 µM, respectively). MMP408 (1 µM) inhibits the proliferation, colony formation, and migration of primary human adamantinomatous craniopharyngioma (ACP) cells.² MMP408 decreases MMP-12 levels, macrophage and lymphocyte bronchoalveolar lavage fluid (BALF) infiltration, and airway hyperresponsiveness in mouse models of respiratory syncytial virus (RSV) infection.³ It decreases ocular collagen-positive lesion size and macrophage accumulation in a mouse model of subretinal fibrosis at 5 mg/kg.⁴

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1. Li, W., Li, J., Wu, Y., et al. A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): Discovery of (S)-2-(8-(methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408). J. Med. Chem. 52(7), 1799-1802 (2009).

2. Li, M., Zhou, L., Li, S., et al. MMP12 is a potential therapeutic target for adamantinomatous craniopharyngioma: Conclusions from bioinformatics analysis and in vitro experiments. Oncol. Lett. 22(1), 536 (2021).

3. Long, X., Li, S., Xie, J., et al. MMP-12-mediated by SARM-TRIF signaling pathway contributes to IFN-γ-independent airway inflammation and AHR post RSV infection in nude mice. Respir. Res. 16(1), 11 (2015).

4. Yi, C., Liu, J., Deng, W., et al. Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis. J. Neuroinflammation 19(1), 78 (2022).