Background:

GM 6001 is a broad-spectrum inhibitor of MMP with Ki values of 0.4nM, 0.5nM, 27nM, 0.1nM and 0.2nM, respectively for MMP-1,2,3,8 and 9 [1].

MMPs are divided into 4 subfamilies: stromelysins, gelatinases, membrane-type MMPs, and collagenases. They play major roles in mediating the effects of IL-1 during meniscal healing. As an inhibitor of MMP, GM 6001 is reported to enhance the repair of meniscal lesions in an inflammatory microenvironment. MMPs also play roles in the transactivation of EGFR induced by GPCR agonists. It is reported that treatment of GM 6001 inhibits the phosphorylation of EGFR as well as the activation of ERK induced by bombesin or LPA. The DNA synthesis induced by bombesin or LPA is also attenuated by GM 6001 since the activity of MMP is required for the GPCR-induced late response mitogenic signaling [1, 2].

参考文献:
[1] McNulty AL, Weinberg JB, Guilak F. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res. 2009 Jun;467(6):1557-67.
[2] Santiskulvong C, Rozengurt E. Galardin (GM 6001), a broad-spectrum matrix metalloproteinase inhibitor, blocks bombesin- and LPA-induced EGF receptor transactivation and DNA synthesis in rat-1 cells. Exp Cell Res. 2003 Nov 1;290(2):437-46.