GlaxoSmithKline, Diseases of the Developing World, Madrid, Spain.
Curr Top Med Chem. 2012;12(5):408-44. doi: 10.2174/156802612799362913.
Falcipains are Plasmodium falciparum cysteine proteases involved in different processes of the erythrocytic cycle of the malaria parasite like hydrolysis of host hemoglobin, erythrocyte invasion, and erythrocyte rupture. These proteases constitute promising targets in the search for novel therapies that would ease the burden caused by the increasing resistance to current antimalarial drugs. Despite biochemical characterization of four falcipains so far, the search for new falcipain inhibitors has been limited to falcipain-2 and/ or falcipain-3, due to their interesting hemoglobinase capacity and the ample availability of tools to study them. We describe progress towards the discovery of promising falcipain inhibitors, in the light of their drug-like properties and the effect of the inhibition of several of these cysteine proteases. Some important aspects to focus on future development of falcipain inhibition are also discussed.
疟原虫裂殖子蛋白是疟原虫半胱氨酸蛋白酶，参与疟原虫红细胞周期的不同过程，如宿主血红蛋白水解、红细胞入侵和红细胞破裂。这些蛋白酶是寻找新疗法的有希望的靶点，可以减轻当前抗疟药物日益增加的耐药性所带来的负担。尽管迄今为止已经对四种疟原虫裂殖子蛋白进行了生化特征描述，但由于它们具有有趣的血红蛋白酶活性和大量可用于研究它们的工具，因此对新的疟原虫裂殖子蛋白抑制剂的研究仅限于疟原虫裂殖子蛋白-2 和/或疟原虫裂殖子蛋白-3。我们根据它们的类药性和抑制几种半胱氨酸蛋白酶的效果，描述了发现有前途的疟原虫裂殖子蛋白抑制剂的进展。还讨论了未来疟原虫裂殖子蛋白抑制开发的一些重要关注点。
