Cheng Yan-Ho, Xia Weiliang, Wong Elissa W P, Xie Qian R, Shao Jiaxiang, Liu Tengyuan, Quan Yizhou, Zhang Tingting, Yang Xiao, Geng Keyi, Silvestrini Bruno, Cheng Chuen-Yan
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Ave, New York, New York 10065, United States of America.
Recent Pat Endocr Metab Immune Drug Discov. 2015;9(2):63-73. doi: 10.2174/1872214809666151029113043.
Adjudin has been explored as a male contraceptive for the last 15 years since its initial synthesis in the late 1990s. More than 50 papers have been published and listed in PubMed in which its mechanism that induces exfoliation of germ cells from the seminiferous epithelium, such as its effects on actin microfilaments at the apical ES (ectoplasmic specialization, a testis-specific actin-rich anchoring junction) has been delineated.
Recent studies have demonstrated that, besides its activity to induce germ cell exfoliation from the seminiferous epithelium to cause reversible infertility in male rodents, adjudin possesses other biological activities, which include anti-cancer, anti-inflammation in the brain, and anti-ototoxicity induced by gentamicin in rodents. Results of these findings likely spark the interest of investigators to explore other medical use of this and other indazole-based compounds, possibly mediated by the signaling pathway(s) in the mitochondria of mammalian cells following treatment with adjudin. In this review, we carefully evaluate these recent findings.
Papers published and listed at www.pubmed.org and patents pertinent to adjudin and its related compounds were searched. Findings were reviewed and critically evaluated, and summarized herein.
Adjudin is a novel compound that possesses anti-spermatogenetic activity. Furthermore, it possesses anti-cancer, anti-inflammation, anti-neurodegeneration, and anti-ototoxicity activities based on studies using different in vitro and in vivo models.
Studies on adjudin should be expanded to better understand its biological activities so that it can become a useful drug for treatment of other ailments besides serving as a male contraceptive.
自20世纪90年代末首次合成以来,过去15年中已对阿地金作为男性避孕药进行了探索。已发表50多篇论文并列入PubMed,其中描述了其诱导生殖细胞从生精上皮脱落的机制,例如其对顶端外质特化(ectoplasmic specialization,一种睾丸特异性富含肌动蛋白的锚定连接)处肌动蛋白微丝的影响。
最近的研究表明,除了具有诱导生殖细胞从生精上皮脱落从而导致雄性啮齿动物可逆性不育的活性外,阿地金还具有其他生物学活性,包括抗癌、脑内抗炎以及对啮齿动物庆大霉素诱导的耳毒性的拮抗作用。这些发现的结果可能会激发研究人员探索该化合物以及其他基于吲唑的化合物的其他医学用途,这可能是由阿地金处理后哺乳动物细胞线粒体中的信号通路介导的。在本综述中,我们仔细评估了这些最新发现。
检索了在www.pubmed.org上发表并列出的与阿地金及其相关化合物有关的论文和专利。对研究结果进行了综述、严格评估并在此进行总结。
阿地金是一种具有抗精子发生活性的新型化合物。此外,基于使用不同体外和体内模型的研究,它还具有抗癌、抗炎、抗神经退行性变和抗耳毒性活性。
应扩大对阿地金的研究,以更好地了解其生物学活性,以便它除了作为男性避孕药外,还能成为治疗其他疾病的有用药物。