Granchi Carlotta, Caligiuri Isabella, Minutolo Filippo, Rizzolio Flavio, Tuccinardi Tiziano
a Department of Pharmacy , University of Pisa , Pisa , Italy.
b Unit of Pathology, Department of Molecular Biology and Translational Research , National Cancer Institute and Center for Molecular Biomedicine , Aviano , Pordenone , Italy.
Expert Opin Ther Pat. 2017 Dec;27(12):1341-1351. doi: 10.1080/13543776.2018.1389899. Epub 2017 Oct 20.
Monoacylglycerol lipase is a serine hydrolase that plays a major role in the degradation of the endocannabinoid 2-arachidonoylglycerol. Because of this key role, selective inactivation of MAGL represents an interesting approach to obtain desirable effects in several diseases. Furthermore, MAGL is upregulated in cancer cells and primary tumors and its inhibition in aggressive breast, ovarian, and melanoma cancer cells impairs cell migration, invasiveness, and tumorigenicity. Areas covered: This review covers patent literature on MAGL inhibitors and their applications published from 2013 to 2017. Expert opinion: MAGL inhibition has gained considerable importance in many therapeutic fields and one compound has been subjected to Phase I studies. Even if a reasonable number of patents have been recently reported, novel MAGL inhibitors are still required, especially novel chemical classes displaying a reversible mechanism of action.
单酰甘油脂肪酶是一种丝氨酸水解酶，在内源性大麻素2-花生四烯酸甘油酯的降解过程中发挥着主要作用。由于这一关键作用，单酰甘油脂肪酶的选择性失活成为在多种疾病中获得理想效果的一种有趣方法。此外，单酰甘油脂肪酶在癌细胞和原发性肿瘤中上调，在侵袭性乳腺癌、卵巢癌和黑色素瘤癌细胞中对其进行抑制会损害细胞迁移、侵袭性和致瘤性。涵盖领域：本综述涵盖了2013年至2017年发表的关于单酰甘油脂肪酶抑制剂及其应用的专利文献。专家观点：单酰甘油脂肪酶抑制在许多治疗领域已变得相当重要，一种化合物已进入I期研究。即使最近已报道了相当数量的专利，但仍需要新型单酰甘油脂肪酶抑制剂，尤其是具有可逆作用机制的新型化学类别。
