Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis
Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis
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DOI：
10.1016/j.ijpara.2017.08.006
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发表时间：
2017-10-01
影响因子：
4
通讯作者：
Van Voorhis, Wesley C.
中科院分区：
文献类型：
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作者：
Hulverson, Matthew A.;Choi, Ryan;Van Voorhis, Wesley C.
已经对碰撞激酶抑制剂的安全性和有效性进行了改进，并且它们正在向人类和动物用于治疗隐孢子虫病的方向发展。随着对用于隐孢子虫病治疗的碰撞激酶抑制剂药效学的理解的增加，已经清楚的是，用于功效的更好的化合物不一定需要大量的全身暴露。我们现在有一个碰撞激酶抑制剂，减少全身暴露，可接受的安全参数，并在小鼠和新生小牛模型的隐孢子虫病的疗效。潜在的心脏毒性是监测这种冲击激酶抑制剂的限制性安全性参数。这种化合物是一种有前途的隐孢子虫病治疗在动物和人类的临床前铅。(C)2017年澳大利亚寄生虫学会。由爱思唯尔有限公司出版。保留所有权利。
Improvements have been made to the safety and efficacy of bumped kinase inhibitors, and they are advancing toward human and animal use for treatment of cryptosporidiosis. As the understanding of bumped kinase inhibitor pharmacodynamics for cryptosporidiosis therapy has increased, it has become clear that better compounds for efficacy do not necessarily require substantial systemic exposure. We now have a bumped kinase inhibitor with reduced systemic exposure, acceptable safety parameters, and efficacy in both the mouse and newborn calf models of cryptosporidiosis. Potential cardiotoxicity is the limiting safety parameter to monitor for this bumped kinase inhibitor. This compound is a promising pre-clinical lead for cryptosporidiosis therapy in animals and humans. (C) 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.