Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.
Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.
复制标题
抑制APE 1/Ref-1治疗新生血管性眼病：从生物学到治疗
DOI：
10.3390/ijms221910279
复制
发表时间：
2021-09-24
影响因子：
5.6
通讯作者：
Corson TW
中科院分区：
文献类型：
--
作者：
Hartman GD;Lambert-Cheatham NA;Kelley MR;Corson TW
糖尿病性视网膜病变（PDR）、新生血管性年龄相关性黄斑变性（nvAMD）、早产儿视网膜病变（ROP）和其他眼部疾病的特征在于视网膜和/或脉络膜新生血管形成，最终导致全世界数百万人的视力丧失。nvAMD和PDR与老龄化有关，随着全球中位年龄和预期寿命的持续上升，预计受影响的人数将增加。随着患病率的增加，针对多个途径的新生血管性眼病的新型口服生物可利用疗法的开发至关重要，因为目前通过玻璃体内注射递送的抗血管内皮生长因子（VEGF）治疗伴随快速耐受、高治疗负担和并发症风险。一个潜在的靶标是脱嘌呤/脱嘧啶核酸内切酶1/还原氧化因子1（APE 1/Ref-1）。多功能蛋白APE 1/Ref-1可通过其氧化还原调节转录因子激活活性的抑制剂靶向调节新生血管性眼病中的血管生成、炎症、氧化应激反应和细胞周期;这些抑制剂在其他组织中也具有神经保护作用。一种APE 1/Ref-1小分子抑制剂已经在癌症、PDR和糖尿病黄斑水肿的临床试验中。正在努力开发更多的抑制剂。APE 1/Ref-1是治疗靶向新生血管性眼病和减轻与抗VEGF玻璃体内注射相关的负担的新候选物。
Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1). The multifunctional protein APE1/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections.
登录
查看更多内容
影响因子：
--
作者：
Batliwala S;Xavier C;Liu Y;Wu H;Pang IH
通讯作者：
Pang IH
当前有关早产视网膜病变的更新：筛查和治疗。
影响因子：
3.6
作者：
Chen J;Stahl A;Hellstrom A;Smith LE
通讯作者：
Smith LE
视网膜和脉络膜血管生成：新靶点综述。
影响因子：
2.3
作者：
Cabral T;Mello LGM;Lima LH;Polido J;Regatieri CV;Belfort R Jr;Mahajan VB
通讯作者：
Mahajan VB
多功能APE1 DNA Repair-Redox信号蛋白是人类疾病中的药物靶标。
影响因子：
7.4
作者：
Caston RA;Gampala S;Armstrong L;Messmann RA;Fishel ML;Kelley MR
通讯作者：
Kelley MR
影响因子：
3.7
作者：
Cesaratto L;Codarin E;Vascotto C;Leonardi A;Kelley MR;Tiribelli C;Tell G
通讯作者：
Tell G