Matrix metallopeptidases (MMPs) are a kind of metalloproteinase which belongs to calcium-dependent zinc endopeptidase. Specifically, these enzymes can degrade all kinds of extracellular matrix proteins, but they can also process many bioactive molecules. Besides, they are known to be involved in the cleavage of cell surface receptors, the release of apoptotic ligands such as fas ligands, and the inactivation of chemokines/cytokines. Moreover, MMPs are one of the main factors of cancer progression and metastasis. This has led to the development of biosensors for the detection of these enzymes. Furthermore, MMPs play a role in the extracellular environment of cells and degrade matrix and non-matrix proteins. They play an important role in morphogenesis, wound healing, tissue repair, and response to injury and remodeling in disease progression. CP-471474 is an orally active and pan MMP inhibitor.
CP-471474 is an orally active and pan MMP inhibitor.
How does brd3308 work on the target? Let’s study it together. In the beginning, CP-471474 is an orally active and pan MMP inhibitor. Meanwhile, CP-471474 has IC50 values of 1170 nM (MMP-1), 0.7 nM (MMP-2), 16 nM (MMP-3), 13 nM (MMP-9) and 0.9 nM (MMP-13), respectively.
In addition, CP-471474 plasma levels following subcutaneous injection are 2,020 ng/mL (1 h postdose) to 160 ng/mL (6 h postdose) in Guinea pigs. Nonetheless, CP-471474 significantly reduces both the extent and severity of inflammation at 2 months in Guinea pigs. At 4 months, a spontaneous reduction of the inflammatory response is observed in both treated and untreated animals. Consequently, no difference is observed between both. Interestingly, CP-471474 significantly decreases the destructive lesions mainly at 2 months and also at 4 months. Particularly, CP-47147 showed an increase of both pro-MMP-9 and its active form (lanes 5 to 8) as compared with control animals.
Last but not the least, CP-471474 treatment reduced 50% MMP-1 protein at 2 months and 4 months. Obviously, the ability of CP-471474 to reduce MMP-9 activity in BAL fluid is consistent with its in vitro activity against this enzyme. Importantly, CP-471474 might provide protection against elastin degradation by blocking the MMP component of elastase activity due to MMP-2 and MMP-12.
All in all, CP-471474 is an orally active and pan MMP inhibitor.
References:
Moisés Selman, et al. Chest. 2003 May;123(5):1633-41.