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These compounds have good oral bioavailability and properties that promote them to be a good candidate for a subtype inhibitor of MMP-13 based diseases and future development. [7] Pyrimidine dicarboxamides are highly selective MMP-13 inhibitors. In the S1’ pocket of MMP-13 is an S1’ side pocket that is unique to the matrix metalloproteiase.
[5] [6] It is a member of the matrix metalloproteinase (MMP) family. Like most MMPs, it is secreted as an inactive pro-form. [7] MMP-13 has a predicted molecular weight around 54 kDa. [8] It is activated once the pro-domain is cleaved, leaving an active enzyme composed of the catalytic domain and the hemopexin-like domain . Although the actual ...
MMP-11 shows more similarity to the MT-MMPs, is convertase-activatable and is secreted therefore usually associated to convertase-activatable MMPs. Substrates include Col IV, fibronectin, laminin, aggrecan MMP12: Macrophage metalloelastase: HME, ME, MME, MMP-12: secreted: Substrates include elastin, fibronectin, Col IV MMP13: Collagenase 3 ...
The most notorious endogenous metalloproteinases are tissue inhibitors of metalloproteinases, followed by cartilage-derived angiogenesis inhibitors. Exogenous matrix metalloproteinase inhibitors were developed as anticancer drugs. [2] Examples include: Batimastat; Cipemastat; Ilomastat; Marimastat; Prinomastat; Rebimastat; Tanomastat
Overall, all MMPs are inhibited by TIMPs once they are activated, but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in their latent form. The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP , a membrane-anchored MMP.
The collective MMP family is capable of degrading all known ECM macromolecules. MMP activity is regulated at the level of transcription, post-translationally by proteolytic cleavage, and by endogenous inhibitors known as tissue inhibitors of metalloproteinases (TIMPs). The role of matrix metalloproteinases and TIMPs in several pathological ...