Department of Pharmacy, School of Health Sciences, University of Patras, Greece.
Trends Pharmacol Sci. 2012 Dec;33(12):623-34. doi: 10.1016/j.tips.2012.09.005. Epub 2012 Oct 19.
Kallikrein-related peptidases (KLKs) constitute a family of 15 serine proteases. Recent studies have shed light on key physiological functions of KLK enzymes and implicate their deregulation in major human pathologies such as neurodegenerative and inflammatory diseases, skin conditions, asthma, and cancer. Consequently, KLKs have emerged as novel targets for pharmacological intervention. Given the pleiotropic roles of KLKs, both activators and inhibitors of KLK activities are of therapeutic interest. For example, inhibitors of hyperactive KLKs in the epidermis would be effective against excess skin desquamation and inflammation, whereas KLK activators could benefit hyperkeratosis caused by diminished KLK proteolysis. Expression of active KLKs by cancer cells and tissues can be exploited to target prodrugs that are proteolytically cleaved to release a cytotoxic compound or a cytolytic toxin at the site of KLK protease activity. Here, we review current approaches for the design and testing of KLK-based therapeutics.
激肽释放酶相关肽酶（KLKs）构成了一个包含 15 种丝氨酸蛋白酶的家族。最近的研究揭示了 KLK 酶的关键生理功能，并表明它们的失调与神经退行性和炎症性疾病、皮肤状况、哮喘和癌症等主要人类疾病有关。因此，KLKs 已成为药物干预的新靶点。鉴于 KLKs 的多效性作用，KLK 活性的激活剂和抑制剂都具有治疗意义。例如，表皮中过度活跃的 KLKs 的抑制剂将有效对抗过度的皮肤脱屑和炎症，而 KLK 激活剂可以有益于因 KLK 蛋白水解减少引起的过度角化。癌细胞和组织中活性 KLKs 的表达可以被利用来靶向前药，这些前药在 KLK 蛋白酶活性部位被蛋白水解切割，释放出细胞毒性化合物或细胞溶解毒素。在这里，我们回顾了基于 KLK 的治疗方法的设计和测试的当前方法。
