Orantinib(Orantinib) - 药物靶点：FGFRs x PDGFR x VEGFR2_在研适应症：乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [4]

靶点

FGFRs x PDGFR x VEGFR2

作用机制

FGFRs拮抗剂(成纤维细胞生长因子受体家族拮抗剂)、PDGFR拮抗剂(血小板衍生生长因子受体拮抗剂)、VEGFR2拮抗剂(血管内皮细胞生长因子受体2拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Taiho Pharmaceutical Co., Ltd.

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

登录后查看时间轴

结构/序列

分子式C18H18N2O3

InChIKeyNHFDRBXTEDBWCZ-UHFFFAOYSA-N

CAS号252916-29-3

关联

13

项与 Orantinib 相关的临床试验

JPRN-JapicCTI-101354

/ Unknown status临床3期

A Randomized, Double-Blind, Placebo-Controlled Phase III Trial Of TSU-68 In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma

开始日期2010-12-01

申办/合作机构

Taiho Pharmaceutical Co., Ltd.

NCT01465464

/ Terminated临床3期

A Randomized, Double-Blind, Placebo-Controlled Phase III Trial Of TSU-68 In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma

The purpose of this study is to compare the overall survival (OS) for Orantinib in combination with transcatheter arterial chemoembolization (TACE) versus placebo in combination with TACE in patients with unresectable hepatocellular carcinoma (HCC).

开始日期2010-12-01

申办/合作机构

Taiho Pharmaceutical Co., Ltd.

JPRN-jRCT2080221054

/ Unknown status临床2期

A Phase II study of TSU-68 in patient with hepatocellular carcinoma who are treated by transcatheter arterial chemoembolization (TACE)

开始日期2010-04-01

申办/合作机构

Taiho Pharmaceutical Co., Ltd.

100 项与 Orantinib 相关的临床结果

登录后查看更多信息

100 项与 Orantinib 相关的转化医学

登录后查看更多信息

100 项与 Orantinib 相关的专利（医药）

登录后查看更多信息

136

项与 Orantinib 相关的文献（医药）

2025-01-02·Autophagy

BIN1 deficiency enhances ULK3-dependent autophagic flux and reduces dendritic size in mouse hippocampal neurons

Article

作者: Sheng, Chengyu ; Li, Qian ; Shi, Huili ; Chen, Tingzhen ; Zhang, Guannan ; Cao, Haifeng ; Gao, Junying ; Ding, Shixin ; Chen, Sijia ; Zhang, Yanli ; Jin, Yuxi ; Xiao, Ming ; Sun, Huaiqing ; Zhao, Lin

Genome-wide association studies identified variants around the BIN1 (bridging integrator 1) gene locus as prominent risk factors for late-onset Alzheimer disease. In the present study, we decreased the expression of BIN1 in mouse hippocampal neurons to investigate its neuronal function. Bin1 knockdown via RNAi reduced the dendritic arbor size in primary cultured hippocampal neurons as well as in mature Cornu Ammonis 1 excitatory neurons. The AAV-mediated Bin1 RNAi knockdown also generated a significant regional volume loss around the injection sites at the organ level, as revealed by 7-Tesla structural magnetic resonance imaging, and an impaired spatial reference memory performance in the Barnes maze test. Unexpectedly, Bin1 knockdown led to concurrent activation of both macroautophagy/autophagy and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1). Autophagy inhibition with the lysosome inhibitor chloroquine effectively mitigated the Bin1 knockdown-induced dendritic regression. The subsequent molecular studydemonstrated that increased expression of ULK3 (unc-51 like kinase 3), which is MTOR-insensitive, supported autophagosome formation in BIN1 deficiency. Reducing ULK3 activity with SU6668, a receptor tyrosine kinase inhibitor, or decreasing neuronal ULK3 expression through AAV-mediated RNAi, significantly attenuated Bin1 knockdown-induced hippocampal volume loss and spatial memory decline. In Alzheimer disease patients, the major neuronal isoform of BIN1 is specifically reduced. Our work suggests this reduction is probably an important molecular event that increases the autophagy level, which might subsequently promote brain atrophy and cognitive impairment through reducing dendritic structures, and ULK3 is a potential interventional target for relieving these detrimental effects.Abbreviations: AV: adeno-associated virus; Aβ: amyloid-β; ACTB: actin, beta; AD: Alzheimer disease; Aduk: Another Drosophila Unc-51-like kinase; AKT1: thymoma viral proto-oncogene 1; AMPK: AMP-activated protein kinase; AP: autophagosome; BafA1: bafilomycin A₁; BDNF: brain derived neurotrophic factor; BIN1: bridging integrator 1; BIN1-iso1: BIN1, isoform 1; CA1: cornu Ammonis 1; CA3: cornu Ammonis 3; CLAP: clathrin and adapter binding; CQ: chloroquine; DMEM: Dulbecco's modified Eagle medium; EGFP: enhanced green fluorescent protein; GWAS: genome-wide association study; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MRI: magnetic resonance imaging; MTOR; mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; PET: positron emission tomography; qRT-PCR: real-time quantitative reverse transcription PCR; ROS: reactive oxygen species; RPS6KB1: ribosomal protein S6 kinase B1; TFEB: transcription factor EB; ULK1: unc-51 like kinase 1; ULK3: unc-51 like kinase 3.

2024-10-01·Journal of Controlled Release

Biomimetic nanocomplex based corneal neovascularization theranostics

Article

作者: Su, Min ; Chen, Chuan ; Han, Yun ; Ye, Jinfa ; Liu, Gang ; Wei, Xingyuan ; Chu, Chengchao ; Wen, Xiaofei ; Pan, Jintao ; Cheng, Yuhang ; Cai, Shundong ; Wu, Yiming

Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV.

2023-05-01·Chemico-Biological Interactions

Structure-based virtual screening of chemical libraries as potential MELK inhibitors and their therapeutic evaluation against breast cancer

Article

作者: Uppal, Sheetal ; Das, Amiya ; Lather, Viney ; Prajapati, Anita ; Agarwal, Pallavi ; Karna, Amarnath ; Pandita, Deepti ; Sharma, Hitesh Kumar

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer.

100 项与 Orantinib 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12072

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
乳腺癌	临床2期	-	Taiho Pharmaceutical Co., Ltd.	-
乳腺癌	临床2期	-	Pfizer Inc.	-
肝细胞癌	临床1期	中国	Taiho Pharmaceutical Co., Ltd.	2010-12-01
不可切除的肝细胞癌	临床1期	韩国	Taiho Pharmaceutical Co., Ltd.	2010-12-01
不可切除的肝细胞癌	临床1期	中国台湾	Taiho Pharmaceutical Co., Ltd.	2010-12-01
不可切除的肝细胞癌	临床1期	日本	Taiho Pharmaceutical Co., Ltd.	2010-12-01
肝癌	临床1期	-	Pfizer Inc.	-
乳腺癌	临床前	日本	Taiho Pharmaceutical Co., Ltd.	-
结直肠癌	药物发现	韩国	Taiho Pharmaceutical Co., Ltd.	-
胃癌	药物发现	日本	Taiho Pharmaceutical Co., Ltd.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01465464 (ORIENTAL, CTgov)	临床3期	不可切除的肝细胞癌	888	Orantinib (TSU-68) (Orantinib)	(顧窪鹹窪觸範廠鏇觸餘) = 積構憲蓋構廠淵憲廠製製夢鏇醖鏇壓艱繭製糧 (膚淵餘範醖鹽廠鏇遞廠, 願積糧艱淵觸選醖觸膚 ~ 簾簾範鹹鑰廠餘齋襯衊) 更多	-	2019-08-07
				Placebo (Placebo)	(顧窪鹹窪觸範廠鏇觸餘) = 顧鬱餘顧選遞淵願衊鑰製夢鏇醖鏇壓艱繭製糧 (膚淵餘範醖鹽廠鏇遞廠, 艱鬱構衊鬱鬱製築積構 ~ 衊積襯範醖簾齋鏇獵鹽) 更多
NCT01465464 (ORIENTAL, Pubmed \| Lancet Gastroenterol Hepatol) 人工标引	临床3期	不可切除的肝细胞癌	889	Orantinib+ cTACE+Orantinib	(構遞蓋艱齋選衊鏇衊積) = 願餘顧膚憲鹽鹹鏇網網艱齋襯構顧鬱願膚餘窪 (淵鏇觸築鑰餘蓋壓構選, 26.5 ~ 34.5) 更多	不佳	2018-01-01
				Placebo	(構遞蓋艱齋選衊鏇衊積) = 廠廠製艱鏇鹽觸糧壓襯艱齋襯構顧鬱願膚餘窪 (淵鏇觸築鑰餘蓋壓構選, 28.4 ~ NR) 更多
JPRN-JapicCTI-121970 (ASCO_GI2013)	临床1期	晚期肝细胞癌	18	TSU-68 plus S-1 combination	(顧餘網餘鬱鏇鏇構蓋觸) = 鏇鹽襯鹹蓋鏇範鬱鏇鹹獵糧構構鏇繭餘壓範鹹 (選觸遞憲遞廠憲獵遞鹹 ) 更多	-	2013-02-01
ASCO2010	临床2期	肝细胞癌	101	TSU-68 400 mg/d	(糧鑰願鏇網鏇廠積壓襯) = 艱鏇襯艱範鹹襯壓憲顧膚齋襯鏇鏇網淵鹽網觸 (衊築衊鑰繭鬱獵憲製鬱 )	-	2010-05-20
				No antitumor therapy	(糧鑰願鏇網鏇廠積壓襯) = 餘壓醖鹽糧簾夢範襯構膚齋襯鏇鏇網淵鹽網觸 (衊築衊鑰繭鬱獵憲製鬱 )
ASCO2008	临床1/2期	晚期肝细胞癌	35	TSU-68 400 mg/d	(願憲衊構艱積醖餘鏇鑰) = 鏇顧夢願顧夢製積繭構膚獵遞壓顧糧願餘網範 (醖襯觸構鬱壓選蓋鹽糧 ) 更多	积极	2008-05-20