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首页> 外文期刊>Pharmaceutical patent analyst >Patent highlights June-July 2018
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Patent highlights June-July 2018

机译：专利亮点2018年6月至7月

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In WO/2017/174716 the present inventors had reported that a protein quantitative trait loci (pQTL) analysis of data from DIOGenes (a pan-European randomized and controlled study investigating the effects of dietary protein and glycemic index on weight loss and its maintenance in obese and overweight families) had revealed a link between branched-chain alpha-keto acid dehydrogenase and the physiological appetite suppressor, leptin (reviewed in Pharm. Patent Anal. 7(2)). The same analysis has found a much less likely link, with Fam64a (CATS), a protein that is overexpressed in malignant tissues and acts as a cell cycle promoter in hypoxic fetal cardiomyocytes but has never been mentioned in the context of obesity. In the DIOGenes data, Fam46a was highly correlated with BAG6, a Bcl2-associated gene for which alternative splicing of its mRNA in subcutaneous fat tissue is known to be strongly influenced by the body mass index. In cultured preadipocytes, Fam64a expression decreases during maturation, to reach a minimum after 7 days while leptin levels rise. Fam64a knockdown did not impact expression of leptin, or of adipocyte differentiation markers. The surprise is the broad range of known molecules that decrease FAM64A expression: various antirheumatic agents, clofibrate, cuprizone, valproate, entinostat (a class I HDAC inhibitor) and even the insecticide fipronil - to name just a few from a long list.
机译：在WO / 2017/1747716中，本发明人报道了一种蛋白质定量性状基因座（PQTL）来自DIOOLES的数据（泛欧随机和对照研究调查膳食蛋白和血糖指数对体重减轻的影响及其维护肥胖和超重家庭揭示了分枝链α-酮酸脱氢酶与生理食欲抑制因素之间的联系（在Pharm.part。专利肛门。7（2））。同样的分析发现，具有FAM64a（猫）的蛋白质，在恶性组织中过表达的蛋白质，并且作为缺氧胎儿心肌细胞中的细胞周期启动子，但在肥胖的背景下从未提及过的蛋白质。在DiOgenes数据中，FAM46A与BAG6高度相关，BCL2相关基因已知在皮下脂肪组织中的其mRNA的替代剪接，受到体重指数的强烈影响。在培养的前脂肪细胞中，FAM64A表达在成熟期间减少，7天后达到最低，而瘦素水平升高。 FAM64A敲低没有影响瘦素的表达，或脂肪细胞分化标志物。令人惊讶的是各种已知分子，可降低FAM64A表达：各种抗胃癌，氯纤维剂，铜酮，丙戊酸，埃替孕汀（I类HDAC抑制剂），甚至是杀虫剂FIPRONIL - 只有一个长名单的少数人。

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