亮蓝G(Brilliant Blue G) - 药物靶点：P2X7 receptor_在研适应症：眼科外科手术，纤维化，肾炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Acid Blue 90、BRILLIANT BLUE G、Brilliant blue G (JAN)

+ [3]

靶点

P2X7 receptor

作用机制

P2X7 receptor拮抗剂(嘌呤P2X7受体拮抗剂)

治疗领域

其他疾病遗传病与畸形眼部疾病+ [1]

在研适应症

眼科外科手术纤维化肾炎+ [1]

非在研适应症-

原研机构

D.O.R.C. Dutch Ophthalmic Research Center (International) BV

在研机构

D.O.R.C. Dutch Ophthalmic Research Center (International) BV

Kyushu University

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2019-12-20),

眼科外科手术

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C47H49N3NaO7S2

InChIKeyRWFXCYWTHJDCMJ-UHFFFAOYSA-N

CAS号6104-58-1

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关联

12

项与亮蓝G 相关的临床试验

JPRN-UMIN000031510

/ SuspendedN/AIIT

Staining with brilliant blue G for the internal limiting membrane - Brilliant blue G stains the internal limiting membrane

开始日期2018-04-01

申办/合作机构-

JPRN-UMIN000031906

/ CompletedN/AIIT

Evaluation of safety of Brilliant Blue G for inner limiting membrane peeling in patients with vitreomacular diseases - Safety of Brilliant Blue G for inner limiting membrane peeling

开始日期2018-03-27

申办/合作机构

Toho University

NCT03020459

/ CompletedN/AIIT

Comparing the Surgical Outcomes of Internal Limiting Membrane Peeling-reposition Versus Peeling in Idiopathic Macular Holes: A Randomized Controlled Trial

To compare the morphologic and functional outcomes of internal limiting membrane peeling-reposition versus peeling in idiopathic macular holes

开始日期2017-01-01

申办/合作机构

上海交通大学医学院附属新华医院

100 项与亮蓝G 相关的临床结果

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100 项与亮蓝G 相关的转化医学

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100 项与亮蓝G 相关的专利（医药）

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785

项与亮蓝G 相关的文献（医药）

2025-02-01·Brain, Behavior, and Immunity

Demyelination of the amygdala mediates psychological stress-induced emotional disorders partially contributed by activation of P2X7R/NLRP3 cascade

Article

作者: Li, Yanning ; Fu, Xiaoliang ; Lin, Dandan ; Jing, Chenchen ; Zhang, Yi

Psychological stress can lead to emotional disorders, such as anxiety and depression; however, the underlying mechanisms are complicated and remain unclear. In this study, we established a mouse psychological stress model using an improved communication box, in which the psychologically stressed mice received visual, auditory, and olfactory emotional stimuli from the mice receiving electric foot shock, thus avoiding physical stress interference. After the 14-day psychological stress paradigm, our mice exhibited a significant increase in depressive and anxious behaviors. We then performed proteomic liquid chromatography-tandem mass spectrometry for proteomic data analysis of the amygdala, and the results demonstrated that differentially expressed proteins were more enriched in myelin-related biological processes, cellular components, and molecular functions, indicating a correlation between psychological stress-induced emotional disorders and amygdala myelin damage. Molecular and morphological evidence further confirmed that psychological stress damages myelin ultrastructure, downregulated myelin basic protein and proteolipid protein expression, and reduced oligodendrocyte proliferation in the amygdala. Moreover, clemastine, an antimuscarinic and antihistaminic compound that has been shown to enhance oligodendrocyte differentiation and myelination, rescued depressive behaviors accompanied by increased oligodendrogenesis. In the amygdala, psychological stress was also noted to activate microglia and increase the levels of NOD-like receptor protein 3 (NLRP3) and the proinflammatory cytokines interleukin 1β and tumor necrosis factor α, as indicated by ELISA and Western blot analyses. Moreover, in stressed mice, the administration of Brilliant Blue G, a purinergic ligand-gated ion channel 7 receptor (P2X7R) antagonist, completely reversed the increases in NLRP3 and cleaved caspase-1 levels and partially prevented amygdala myelin damage. In conclusion, amygdala demyelination may mediate psychological stress-induced emotional disorders, and P2X7R/NLRP3 cascade activation partially contributes to amygdala myelin damage after psychological stress.

2024-12-01·Molecular Immunology

The role and mechanism of P2X7R in cirrhotic cardiomyopathy

Article

作者: Ding, Xu ; Zhou, Yiting ; Shao, Zhenhao ; Dai, Yufei ; Wang, Ruxing ; Wu, Dan ; Luo, Yu ; Yu, Zhiming ; Qian, Lingling ; Zhou, Jiabin

In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated. In our research, a cirrhotic cardiomyopathy animal model was established using mice subjected to bile duct ligation. The expression of the P2X7 receptor was suppressed via intraperitoneal administration of Brilliant Blue G. Cardiac function was evaluated using echocardiographic techniques, while histopathological examination and enzyme-linked immunosorbent assays were employed to assess the presence of inflammation and apoptosis in liver and cardiac tissues. The expression of key proteins, including P2X7, NLRP3, and IL-1β, in the myocardial tissue was quantified by Western blot analysis. Our research has unveiled significant findings in a murine model of liver fibrosis induced by two weeks of bile duct ligation. Notably, we detected escalated levels of liver fibrosis coupled with disruptions in liver blood flow dynamics. Concurrently, there was a marked increase in myocardial inflammation and apoptosis, which adversely affected heart function. Intriguingly, the expression of P2X7 receptors (P2X7R) in cardiac and hepatic tissues was found to be significantly elevated. Targeting and inhibiting the expression of P2X7R not only alleviated myocardial inflammation and apoptosis but also enhanced cardiac performance. Furthermore, this intervention resulted in a noticeable reduction in liver fibrosis. The interplay between the P2X7 and NLRP3 pathways emerges as a pivotal mechanism in the etiology and progression of cirrhotic cardiomyopathy. Our findings suggest that modulating the P2X7-NLRP3 axis could offer promising therapeutic avenues for managing cirrhotic cardiomyopathy.

2024-12-01·Biomedicine & Pharmacotherapy

The analgesic and gastroprotective activities of the three fungal extracts and their possible correlation with the inhibition of the P2X7 receptor

Article

作者: da Silva Frutuoso, Válber ; Miranda, Julliana Alves Azeredo ; Zani, Carlos Leomar ; da Silva Ferreira, Natiele Carla ; Soares-Bezerra, Rômulo José ; Rosa, Luiz Henrique ; Alves, Luiz Anastacio ; de Almeida Alves, Tânia Maria ; Lima-Quaresma, Kátia Regina Ferreira ; Calheiros, Andrea Surrage ; de Souza, Cristiane Zanon

P2X7 is a purinergic receptor physiologically activated by extracellular ATP. Its activation induces proinflammatory responses, including cytokine release, reactive oxygen species formation, and cell death. Previous in vivo experimental models demonstrated that P2X7 blockade has anti-inflammatory effects; however, there are no drugs used in clinical therapy that act on the P2X7 receptor. In the context of inflammatory diseases, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as the first-line treatment; however, their major side effects include stomach ulcer formation, which increases patient morbidity and mortality. Here, we analyzed for the first time the analgesic and gastroprotective activities of three fungal extracts that showed antagonistic effects on P2X7 in vitro. The Antarctic fungal extracts obtained from Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp. were tested in animal models of acute pain and ethanol-induced ulceration. These three extracts reduced paw licking by approximately 50 %, which is related to pain behavior, and reduced the number of stomach ulcers 3-7 times compared with the control (70 % ethanol), making them more efficient than the lansoprazole, an NSAID drug, and Brilliant Blue G (BBG), a known P2X7 antagonist, which only halves the number of ulcers. Furthermore, the extracts also protected the gastric mucosa and significantly reduced the levels of liver and renal enzymes compared with those in the ethanol group. Taken together, the fungal extracts presented both analgesic and possibly anti-inflammatory activities and had a protective effect on the gastric epithelium.

2

项与亮蓝G 相关的新闻（医药）

2024-05-22

·药精通Bio

美国FDA批准的38个小分子药合成路线汇总

深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，联系电话181 1603 6798文章来源：有机合成路线这里小编和大家分享美国食品药品监督管理局 (FDA) 批准上市的38个化学小分子药合成路线，以飨化学和药化从业者，学生和爱好者。第一类（1.1）：抗肿瘤药物1.1.1 Erdafitinib (1)1.1.2 Alpelisib (2)1.1.3 Selinexor (3)1.1.4 Darolutamide (4)1.1.5 Pexidartinib (5)1.1.6 Entrectinib(6)1.1.7 Fedratinib (7)第二类（1.2）：抗菌药1.2.1 亚胺培南/西拉司丁/relebactam (9)1.2.2 Pretomanid (10)1.2.3 Lefamulin (11)1.2.4 Cefiderocol(12)第三类（1.3）：偏头痛治疗药物1.3.1 Lasmiditan (13)1.3.2 Ubrogepant(14)第四类（1.4）：其它治疗药物1.4.1 三氯苯达唑 (triclabendazole, 15)1.4.2 Brexanolone (16)1.4.3 Solriamfetol(17)1.4.4 Siponimod (18)1.4.5 Tafamidis(19) 和tafamidis meglumine1.4.6 Bremelanotide (20)1.4.8 替洛利生 (pitolisant, 22)1.4.9 Upadacitinib (23)1.4.10 Istradefylline (24)1.4.11Tenapanor(25)1.4.12 Trifarotene (26)1.4.13 阿法诺肽 (afamelanotide，27)1.4.14 Elexacaftor(28)/tezacaftor/ivacaftort1.4.15 Givosiran (29)1.4.16 Cenobamate (30)1.4.17 Voxelotor (31)1.4.18 Golodirsen (32)1.4.19Lemborexant (33)1.4.20 Lumateperone tosylate (34)2.1 Ga-68-DOTATOC(35)2.2 Fluorodopa (36)2.3 Air polymer-type A(37)是一种无菌透明凝胶 [polymer-type A(80.97 mg羟乙基纤维素 )，434.80 mg甘油 (85％)和纯净水 ]2.4 Brilliant blue G ophthalmic solution (38)参考文献：中国医药工业杂志Chinese Journal of Pharmaceuticals 2020, 51(1), 吕训磊，周伟澄，林快乐. 免责声明：本文信息来源于网络，本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。END深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话18116036798戳“阅读原文”立即报名多肽药物论坛吧!

上市批准临床结果

2023-03-24

·药时代

FDA批准药物的关键专利特征

专利保护，是新药开发者阻止仿制药竞争，并获取高额回报的保证。从美国食品药品管理局（FDA）橙皮书列表中提取了专利，并评估了专利申请的时间、专利涵盖药物的特征以及其他国家是否获得类似的专利，寻找原研药物关键专利特征。FDA在2019-2020年批准的78个药物中，有10个没有专利，其余68个药物列出了322个不同的专利（中位数为4个）。根据受保护发明的性质，最常见的专利类别是化合物（201；62%），其次是使用方法（195；61%）。从原始药物批准到最终专利到期日的中位时间为10.3年。大约五分之一的专利在世界其他主要司法管辖区没有对应的专利。涵盖新批准药物的专利在很大程度上保护了产品及其用途；专利（而不是非专利排他性）是确保及时阻止仿制药进入市场的关键。FDA于2019-2020年批准的78个小分子药物（2019年48个药物和2020年53个药物）：2019年，有5个药物没有专利：artesunate，copper Cu-64 dotatate (Detectnet)，gallium Ga 68 PSMA-11，nifurtimox (Lampit)，和fluoroestradiol F18 (Cerianna)。2020年，有5个药物没有专利：brilliant blue G ophthalmic solution (TissueBlue)，fluorodopa F18，Ga-68-DOTATOC (Ga-68-DOTATOC)，pretomanid,和triclabendazole (Egaten)。其余68个药物获得了322件专利。每种药物的专利数量中位数为4。最常见的专利申请类别是化合物（n=201；62%），其次是使用方法（n=195；61%）、制造工艺（n=32；10%）和制剂（n=173；54%）或复合制剂（n=13；4%）（图表1）。结果是非互斥的，超过一半（n=188；58%）的专利拥有属于一个以上类别的权利要求。在FDA批准之前，专利的申请时间中位数为5.6年（IQR:3.3–9.2），公告时间中位数为4.5年（IQR:1.3–6.1）。专利申请到药物批准的时间范围从芦比替定/lurbinectedin（在FDA批准前17.6年提交）到塞普替尼/selpercatinib（在FDA审批前2年提交）。在大量专利中，专利申请时间通常与药物开发过程一致，因为化合物权利要求（n=201）在FDA批准药物前的中位数为6.5年（IQR:4-10），而使用方法权利要求（n=195）的专利在FDA批准之前的中位数为5.1年（IQR=3.2-8.4）。在FDA批准药物之前，仅有化合物权利要求专利的申请时间中值为5.7年（IQR:2-8）。图 2019-2020年FDA批准药物的批准日期与最后一项到期专利的到期日期之间的时间差基于所列专利的最新到期日，这些药物的预期专利保护市场独占期为药物批准后10.3年的中位数（IQR:7.2-13.8）。药物批准与专利最新到期日之间的最低时间差为3.7年，而最高时间差为20.3年。队列中的68个药物中有39个（57%）被指定为“孤儿药（Orphan Drug）”，在FDA批准时，39个药物中的33个（85%）的专利保护超过了法规规定的额外的7年市场排他性。所有29个非孤儿药指定药物（100%）的初始专利期超过了五年的哈奇-瓦克斯曼法案新药非专利市场独占期。在批准时，孤儿药指定的药物和普通条件指定药物之间的专利保护期限没有重大差异。在FDA橙皮书列出的322件专利中，有22件（7%）最初颁发给了非公司研究机构。例如，与5件专利相关的一个机构是非美国学术中心（西澳大利亚大学）。大约一半的专利（n=149；46%）的原始专利受让人与FDA列出的申请新药的发起人不同。17件（5%）专利有多名受让人。在322件专利中，52件（16%）在其简单专利家族中没有授予外国专利，因此仅为美国专利。在这52件专利中，34件（65%）在简单专利家族没有外国未决专利申请。在剩余的未决专利申请中（52件中的18件；35%），有5件外国专利申请在欧洲、加拿大或日本被撤回或拒绝。其他13件专利申请仍在审理中。FDA列出的与外国授予的同等专利最常见的国家是日本（n=243；75%），其次是欧洲（n=232；72%）和加拿大（n=183；57%）。没有外国授予专利等效物的专利包括化合物权利要求（55%）、使用方法权利要求（65%）、工艺权利要求（8%）、制剂权利要求（52%）和复合制剂权利要求的专利（2%）。FDA在2019年和2020年批准的涵盖小分子药物的专利大多涵盖了活性成分和使用方法，但也涵盖了多种其他发明。这些专利的有效期通常已经超过了《Hatch-Waxman Act》和《孤儿药法案》的排他性期限。我们预计有些药物未来将申请更多的专利，涵盖药物的次要方面。参考资料：Van de Wiele VL, Torrance AW, Kesselheim AS. Characteristics Of Key Patents Covering Recent FDA-Approved Drugs. Health Aff (Millwood). 2022 Aug;41(8):1117-1124. doi: 10.1377/hlthaff.2022.00002. PMID: 35914209.封面图来源：123rf推荐阅读4轮临床试验结果全矛盾，这减肥药，把积极结果做毁了……3年前，百济神州为了一个冷门靶点花了800万美金，如今......10年时间，临床成功率翻10倍！辉瑞的成功之道在哪里？点击在看，共济新药研发浪潮

专利到期专利无效

100 项与亮蓝G 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10799	-	S01	DB15594

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
眼科外科手术	加拿大	D.O.R.C. Dutch Ophthalmic Research Center (International) BV	-

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
纤维化	临床前	-	-	2013-04-01
肾炎	临床前	-	-	2013-04-01
视网膜变性	临床前	日本	Kyushu University	2011-04-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ARVO2019	N/A	视网膜穿孔	-	brilliant Blue G (No-dye group)	(鏇鹹觸顧鬱餘願構憲築) = The rates of changes in deficiency of EZ at 1 and 6 months compared with baseline in BBG group were significantly greater than those in no dye group 製醖獵遞觸餘製醖網範 (糧膚憲蓋製艱鏇鬱糧獵 ) 更多	-	2019-07-01
				brilliant Blue G (BBG group)
ASN2012	N/A	输尿管梗阻 P2X7 receptor	-	Brilliant Blue G (Sham operated and saline infusion)	鹹壓醖淵膚鬱簾簾範簾(衊蓋膚壓製廠觸鹽鏇選) = 廠壓醖蓋繭選繭積鑰鬱鑰遞積齋製衊蓋遞艱獵 (製醖艱壓鹽構廠範鏇窪 ) 更多	积极	2012-10-30
				Sham and BBG 25mg/kg intravenously (IV)	鹹壓醖淵膚鬱簾簾範簾(衊蓋膚壓製廠觸鹽鏇選) = 餘遞壓艱齋鑰網鹹餘憲鑰遞積齋製衊蓋遞艱獵 (製醖艱壓鹽構廠範鏇窪 ) 更多
ARVO2011	N/A	毒性	-	Brilliant Blue G 1 mg/ml	鹽膚顧鬱範淵齋淵壓糧(選廠蓋獵繭鬱範選膚襯) = 廠網膚餘觸膚獵觸餘積憲構簾選築淵獵積壓鹹 (餘築積鹽膚遞築夢範遞 )	积极	2011-04-01
ARVO2011	N/A	视神经损伤	-	Brilliant Blue G	鏇鬱網鹹襯鏇積積蓋繭(壓鬱憲鹽淵簾顧廠襯齋) = 顧顧餘蓋選構淵膚構淵遞遞膚積鬱築壓鏇衊鏇 (醖願鹽積鹹鹽膚觸簾鹹 ) 更多	-	2011-04-01
				Vehicle (0.9% NaCl)	(簾願夢糧構遞衊憲餘網) = 糧襯築廠餘淵壓願願衊夢選遞齋襯獵繭觸鬱鬱 (積構糧觸衊齋衊艱膚膚 )
PO531 (AAO2010)	N/A	视网膜穿孔辅助	-	Brilliant Blue	(鬱壓繭鬱積網簾壓築齋) = 構夢醖鬱淵鹽壓齋繭繭鹽獵鏇淵願糧鹹築獵憲 (廠蓋襯糧製願鹽積觸衊 ) 更多	-	2010-10-18
				Brilliant Blue	(鬱壓繭鬱積網簾壓築齋) = 夢網膚淵網壓願齋壓窪鹽獵鏇淵願糧鹹築獵憲 (廠蓋襯糧製願鹽積觸衊 ) 更多
ARVO2010	N/A	毒性	8	Brilliant Blue G 1mg/ml	構艱簾壓鑰選齋壓淵網(鹹顧觸蓋構齋繭顧製鏇) = 憲鑰鏇範壓願憲膚艱壓夢製衊糧淵鏇壓獵壓壓 (繭網壓鏇壓襯鏇衊觸憲 ) 更多	积极	2010-04-01
				Brilliant Blue G Staining (SF6 gas tamponade)	構艱簾壓鑰選齋壓淵網(鹹顧觸蓋構齋繭顧製鏇) = 構醖積觸製襯製鏇憲襯夢製衊糧淵鏇壓獵壓壓 (繭網壓鏇壓襯鏇衊觸憲 ) 更多