癌症研究
血管生成
缺氧诱导因子
血管内皮生长因子
生物
缺氧(环境)
抑癌基因
血管母细胞瘤
促红细胞生成素
冯希佩尔-林道病
内科学
医学
内分泌学
癌症
病理
疾病
基因
化学
遗传学
血管内皮生长因子受体
癌变
有机化学
氧气
作者
Vysakh Visweswaran,Keechilat Pavithran
出处
期刊:Current drug research reviews
[Bentham Science]
日期:2022-07-01
卷期号:14 (2): 88-95
被引量:11
标识
DOI:10.2174/2589977514666220401094724
摘要
Von Hippel-Lindau disease is an autosomal dominant disorder characterised by renal cell carcinomas, pancreatic neuroendocrine tumours, central nervous system hemangioblastomas, retinoblastomas, and tumours of the reproductive tract. This disease results from loss of function mutations in the tumour suppressor gene known as the Von Hippel-Lindau gene, located on chromosome 3. Loss of function mutation in the Von Hippel-Lindau gene results in the accumulation of a protein known as a hypoxia-inducible factor, which promotes cellular proliferation and angiogenesis, leading to cancer. Belzutifan inhibits the hypoxia-inducible factor by binding to the Per-ARNT -Sim-B binding pocket on the hypoxia-inducible factor -2α, inhibiting cellular proliferation and angiogenesis. In our thorough literature review, we identified 37 relevant articles. Belzutifan showed clinically meaningful response rates for both Von Hippel-Lindau disease-associated renal cell carcinomas and non-renal cell cancers. The pharmacokinetic profile of belzutifan was much better than its congener molecules due to the optimisation of its dihalide groups from germinal to vicinal. The pharmacodynamic effect of belzutifan was confirmed by its ability to decrease serum erythropoietin, which is a direct result of hypoxia-inducible factor- 2α inhibition. The significant side effects observed were anaemia, hypoxia, fatigue, hypertension, visual impairment and weight gain. Multiple clinical trials are currently underway to determine the role of beluztifan as part of combination regimens in treating Von Hippel-Lindau disease-associated malignancies.
科研通智能强力驱动
Strongly Powered by AbleSci AI