Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.
Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.
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DOI：
10.1002/med.21315
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发表时间：
2014-11
影响因子：
13.3
通讯作者：
Desai UR
中科院分区：
文献类型：
--
作者：
Al-Horani RA;Desai UR
越来越多的证据表明，纤溶酶除了在纤维蛋白切割中起关键作用外，还参与许多生理过程。纤溶酶抑制在预防纤溶酶过度活性引起的不良后果方面至关重要，例如心脏手术后可能会失血。抑肽酶在2008年停用之前被广泛用作抗纤溶药物。氨甲环酸和ε-氨基己酸是目前临床上使用的两种小分子纤溶酶抑制剂。已经设计了几个分子，利用共价但可逆的化学依赖于反应性环己酮、氰弹头和反应性醛多肽。其他主要类别的纤溶酶抑制物包括环多肽模拟物和库尼茨和卡扎尔类型的多肽。纤溶酶的变构抑制剂也被设计出来，包括与纤溶酶kringle结构域结合的小分子赖氨酸类似物(S)和与纤溶酶催化结构域结合的硫酸化氨基聚糖类似物。纤溶酶抑制剂也被探索用于解决其他疾病状态，包括细胞转移、细胞增殖、血管生成和胚胎植入。本综述重点介绍了纤溶酶抑制剂的功能和结构方面，以期推进其设计。
Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical in preventing adverse consequences arising from plasmin overactivity, e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and ε-aminocaproic acid, two small molecule plasmin inhibitors, are currently used in the clinic. Several molecules have been designed utilizing covalent, but reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type. Allosteric inhibitors of plasmin have also been designed including small molecule lysine analogs that bind to plasmin’s kringle domain(s) and sulfated glycosaminoglycan mimetics that bind to plasmin’s catalytic domain. Plasmin inhibitors have also been explored for resolving other disease states including cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This review highlights functional and structural aspects of plasmin inhibitors with the goal of advancing their design.
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影响因子：
4.8
作者：
Bajaj, Madhu S.;Ogueli, Godwin I.;Bajaj, S. Paul
通讯作者：
Bajaj, S. Paul
DOI：
10.1016/j.jtcvs.2011.06.001
发表时间：
2012-05-01
影响因子：
6
作者：
Bokesch, Paula M.;Szabo, Gabor;Levy, Jerrold H.
通讯作者：
Levy, Jerrold H.
DOI：
10.1161/01.atv.12.6.708
发表时间：
1992-06-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
ANONICK, PK;VASUDEVAN, J;GONIAS, SL
通讯作者：
GONIAS, SL
影响因子：
7.3
作者：
Bostrom, Jonas;Grant, J. Andrew;Gustafsson, David
通讯作者：
Gustafsson, David
影响因子：
4.8
作者：
Chand, HS;Schmidt, AE;Kisiel, W
通讯作者：
Kisiel, W