Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present).
Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present).
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DOI：
10.1080/13543776.2020.1705783
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发表时间：
2020-01
影响因子：
6.6
通讯作者：
Al-Horani RA
中科院分区：
文献类型：
--
作者：
Al-Horani RA
抗凝不出血是治疗血栓形成的理想目标，然而，这一目标尚未实现。目前所有的抗凝剂都与严重出血有关，这限制了它们的安全使用。遗传学和药理学研究结果表明，因子XIa是血栓形成的关键因素，但它在止血方面是一个相对边缘的因素。因此，因子XIa及其酶原为开发低出血风险的抗凝剂提供了独特的机会。自2016年以来，一项专利文献调查检索到了50多项关于发现靶向因子XI（a）的新型疗法的专利。已经开发了小分子、单克隆抗体、寡核苷酸和多肽来抑制因子XI（a）。许多抑制剂处于早期开发阶段，很少在临床试验中进行评估。因子XI（a）作为开发有效和更安全的抗凝剂的药物靶点正在被积极追求。虽然许多专利声称因子XI（a）抑制剂是在2016年之前提交的，但最近的文献显示出适度下降的趋势。尽管如此，更多的药物已进入不同水平的临床试验。这些药物利用不同的机制策略进行抑制。虽然需要进一步的开发，但将这些药物中的一种或多种应用于临床将改变抗凝治疗。
Anticoagulation without bleeding is an ideal goal in treating thrombosis, however, this goal has not been achieved. All current anticoagulants are associated with significant bleeding which limits their safe use. Genetic and pharmacological findings indicate that factor XIa is a key player in thrombosis, yet it is a relatively marginal one in hemostasis. Thus, factor XIa and its zymogen offer a unique opportunity to develop anticoagulants with low bleeding risk. A survey of patent literature has retrieved more than 50 patents on the discovery of novel therapeutics targeting factor XI(a) since 2016. Small molecules, monoclonal antibodies, oligonucleotides, and polypeptides have been developed to inhibit factor XI(a). Many inhibitors are in early development and few have been evaluated in clinical trials. Factor XI(a) is being actively pursued as a drug target for the development of effective and safer anticoagulants. Although many patents claiming factor XI(a) inhibitors were filed prior to 2016, recent literature reveals a moderately declining trend. Nevertheless, more agents have entered different levels of clinical trials. These agents exploit diverse mechanistic strategies for inhibition. Although further development is warranted, reaching one or more of these agents to the clinic will transform the anticoagulation therapy.
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影响因子：
13.3
作者：
Al-Horani RA;Afosah DK
通讯作者：
Afosah DK
影响因子：
6.6
作者：
Al-Horani RA;Desai UR
通讯作者：
Desai UR
DOI：
10.1056/nejmoa1405760
发表时间：
2015-01-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Büller HR;Bethune C;Bhanot S;Gailani D;Monia BP;Raskob GE;Segers A;Verhamme P;Weitz JI;FXI-ASO TKA Investigators
通讯作者：
FXI-ASO TKA Investigators
影响因子：
7.5
作者：
Berliner, JI;Rybicki, AC;Billett, HH
通讯作者：
Billett, HH
影响因子：
6.7
作者：
Choi, Sharon H.;Smith, Stephanie A.;Morrissey, James H.
通讯作者：
Morrissey, James H.