Marimastat

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor (IC₅₀s = 5, 6, 230, 16, and 3 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively).¹ It also binds to a recombinantly expressed catalytic domain of human MMP-14 (MMP-14_cat; K_i = 2.1 nM) and inhibits gelatinases (IC₅₀s = 3–6 nM), fibroblast collagenase (IC₅₀ = 5 nM), and matrylisin (IC₅₀ = 16 nM).² It inhibits peritoneal dissemination of implanted human gastric carcinoma TMK-1 cells in nude mice (18 mg/kg per day) but does not affect TMK-1 viability in vitro, providing only 2.64% inhibition when used at a concentration of 10 μM.³ Marimastat inhibits lymph node metastasis in an oral squamous cell carcinoma (OSCC) OSC-19 mouse xenograft model (30 mg/kg per day).⁴ It also delays tumor growth of human head and neck squamous cell SCC-1 xenografts in nude mice alone and when combined with chemoradiation when administered at a dose of 8.7 mg/kg per day.⁵ Marimastat is an inhibitor of tumor necrosis factor alpha (TNF-α) convertase (TACE), which catalyzes pro-TNF-α conversion into TNF-α (IC₅₀s = 3.8 and 7,000 nM for purified TACE and whole blood, respectively).⁶

WARNING This product is not for human or veterinary use.

1. Rasmussen, H.S., and McCann, P.P. Matrix metalloproteinase inhibition as a novel anticancer strategy: A review with special focus on batimastat and marimastat. Pharmacol. Ther. 75(1), 69-75 (1997).

2. Toth, M., Bernardo, M.M., Gervasi, D.C., et al. Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of pro-MMP-2. The Journal of Biological Chemisty 275(52), 41415-41423 (2000).

3. Kimata, M., Otani, Y., Kubota, T., et al. Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice. Jpn. J. Cancer Res. 93(7), 834-841 (2002).

4. Maekawa, K., Sato, H., Furukawa, M., et al. Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin. Exp. Metastasis 19(6), 513-518 (2002).

5. Skipper, J.B., McNally, L.R., Rosenthal, E.L., et al. In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts. ORL J. Otorhinolaryngol. Relat. Spec. 71(1), 1-5 (2009).

6. Barlaam, B., Bird, T.G., Lambert-Van Der Brempt, C., et al. New α-substituted succinate-based hydroxamic acids as TNFα convertase inhibitors. J. Med. Chem. 42(23), 4890-4908 (1999).