Howland Robert H
J Psychosoc Nurs Ment Health Serv. 2015 Mar;53(3):13-6. doi: 10.3928/02793695-20150219-01.
Fumagillin, an antimicrobial compound first isolated in 1949 from the fungus Aspergillus fumigatus, four decades later was unexpectedly found to inhibit angiogenesis. Interest in developing angiogenesis inhibitor drugs as possible treatments for cancer led to the synthesis of analogs of fumagillin. Preclinical studies of various analog drugs confirmed that they inhibited angiogenesis, but they also were associated with weight loss as an adverse effect. Because adipose tissue can grow and regress throughout adulthood, is highly vascularized, and has angiogenic properties, interest in investigating anti-angiogenic agents in animal models of obesity found that fumagillin analogs caused dose-dependent reversible weight reduction and adipose tissue loss. Beloranib, a fumagillin analog that is an angiogenesis inhibitor and associated with decreased adiposity in animals, has been studied in phase I clinical trials for cancer. It is currently being investigated for the treatment of obesity and related conditions. Three phase I and three phase II studies found significant degrees of weight loss and acceptable tolerability for beloranib compared to placebo, justifying further clinical development of the drug for obesity.
烟曲霉素是一种抗菌化合物，于1949年首次从烟曲霉中分离出来，四十年后意外地发现它能抑制血管生成。开发血管生成抑制剂药物作为癌症可能治疗方法的兴趣促使人们合成了烟曲霉素类似物。各种类似物药物的临床前研究证实它们能抑制血管生成，但它们也与体重减轻这一不良反应有关。由于脂肪组织在成年期可生长和消退，血管高度丰富且具有血管生成特性，因此在肥胖动物模型中研究抗血管生成药物的兴趣发现，烟曲霉素类似物会导致剂量依赖性的可逆体重减轻和脂肪组织减少。贝罗尼布是一种烟曲霉素类似物，是一种血管生成抑制剂，在动物中与肥胖减轻有关，已在癌症的I期临床试验中进行了研究。目前正在对其治疗肥胖及相关病症进行研究。三项I期和三项II期研究发现，与安慰剂相比，贝罗尼布有显著的体重减轻程度且耐受性可接受，这为该药物用于肥胖的进一步临床开发提供了依据。
