New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies.
New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies.
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DOI：
10.1155/2011/191670
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发表时间：
2011
影响因子：
3
通讯作者：
Dransfield DT
中科院分区：
文献类型：
--
作者：
Devy L;Dransfield DT
MMP干预策略由于严重的毒性而获得了有限的临床成功。特别是，用广谱MMP抑制剂（MMPIs）治疗引起肌肉骨骼疼痛和炎症。选择性对于实现MMPIs的临床潜力可能是至关重要的。在这里，我们回顾发现，精确定位膜结合MMPs作为介质的机制，癌症和炎症，并作为可能的治疗目标，预防/治疗这些疾病。我们讨论了使用高选择性抑制剂靶向这些治疗性蛋白酶的策略（即，人阻断抗体）。
MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs) caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies) against individual membrane-bound MMPs.