LoGiudice Nicole, Le Linh, Abuan Irene, Leizorek Yvette, Roberts Sigrid C
Pacific University School of Pharmacy, Hillsboro, OR 97123, USA.
Med Sci (Basel). 2018 Feb 8;6(1):12. doi: 10.3390/medsci6010012.
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC is potentially a drug target for any disease state where rapid growth is a key process leading to pathology. The compound was originally discovered as an anticancer drug, but its effectiveness was disappointing. However, DFMO was successfully developed to treat African sleeping sickness and is currently one of few clinically used drugs to combat this neglected tropical disease. The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa. In recent years, renewed interest in DFMO for hyperproliferative diseases has led to increased research and promising preclinical and clinical trials. This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma.
氟化鸟氨酸类似物α-二氟甲基鸟氨酸（DFMO，依氟鸟氨酸，奥尼地尔）是鸟氨酸脱羧酶（ODC）的不可逆自杀性抑制剂，ODC是多胺生物合成的首个限速酶。普遍存在且必不可少的多胺具有多种功能，但对快速增殖的细胞尤为重要。因此，对于任何以快速生长作为导致病变的关键过程的疾病状态而言，ODC都有可能成为药物靶点。该化合物最初是作为抗癌药物被发现的，但其疗效并不理想。然而，DFMO已成功用于治疗非洲昏睡病，并且是目前用于对抗这种被忽视的热带病的少数几种临床用药之一。美国食品药品监督管理局（FDA）批准的DFMO的另一项应用是作为脱毛膏Vaniqa的活性成分。近年来，人们对DFMO治疗增殖性疾病的兴趣再度燃起，这导致了相关研究的增加以及有前景的临床前和临床试验。本综述探讨了DFMO在治疗非洲昏睡病和多毛症方面的应用，以及其作为预防结直肠癌和神经母细胞瘤的化学预防剂和化疗剂的潜力。
