Beta Lapachone(Beta Lapachone) - 药物靶点：NQO1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [6]

靶点

NQO1

作用机制

NQO1抑制剂(苯醌还原酶-1抑制剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

腺癌晚期恶性实体瘤纤维化+ [9]

原研机构

Arisyn Therapeutics Inc

在研机构-

非在研机构

Arisyn Therapeutics Inc

Yungjin Pharm. Co., Ltd.

ArQule, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C15H14O3

InChIKeyQZPQTZZNNJUOLS-UHFFFAOYSA-N

CAS号4707-32-8

关联

13

项与 Beta Lapachone 相关的临床试验

NCT02338856

/ Completed临床1期

A Phase I Clinical Trial to Evaluate the Pharmacokinetics and Safety of MB12066 in Healthy Male Volunteers

The purpose of this study is to investigate the safety and tolerability of MB12066 after multiple dose and to investigate the pharmacokinetic characteristics of MB12066 after multiple dose.

开始日期2015-01-01

申办/合作机构

Yungjin Pharm. Co., Ltd.

NCT02029586

/ Terminated临床2期

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, 12 Weeks, Therapeutic Exploratory Phase 2 Clinical Study to Evaluate the Safety and Efficacy of MB12066 in Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Except Cirrhosis

This is a controlled study to determine the effectiveness and safety of MB12066 in the treatment of adult patients with Nonalcoholic Fatty Liver Disease(NAFLD) except cirrhosis.

开始日期2013-01-01

申办/合作机构

Yungjin Pharm. Co., Ltd.

NCT01444677

/ Completed临床1期

A Dose Block-randomized, Double-blind, Placebo-controlled, Single or Multiple Dosing, Dose-escalation Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetic Characteristics of MB12066 in Healthy Male Subjects

The purpose of this study is to investigate the safety and tolerability of MB12066 after a single or multiple oral dose and to investigate the pharmacokinetic characteristics of MB12066 after a single or multiple oral dose.

开始日期2011-04-01

申办/合作机构

Yungjin Pharm. Co., Ltd.

[+1]

100 项与 Beta Lapachone 相关的临床结果

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100 项与 Beta Lapachone 相关的转化医学

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100 项与 Beta Lapachone 相关的专利（医药）

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929

项与 Beta Lapachone 相关的文献（医药）

2025-06-01·Biomaterials

Hybrid membrane based biomimetic nanodrug with high-efficient melanoma-homing and NIR-II laser-amplified peroxynitrite boost properties for enhancing antitumor therapy via effective immunoactivation

Article

作者: Zha, Yongchao ; Xue, Wei ; Yu, Siming ; Zeng, Yina ; Lin, Qi ; Zhang, Yu

Owing to the excellent stability, anticancer activity and immunogenicity, peroxynitrite (ONOO^-) has been gained enormous interests in cancer therapy. Nevertheless, precise delivery and control release of ONOO^- in tumors remains a big challenge. Herein, B16F10 cancer cell membrane/liposome hybrid membrane (CM-Lip) based biomimetic nanodrug with high-efficient tumor-homing and NIR-II laser controlled ONOO^- boost properties was designed for melanoma treatment. Briefly, NIR-II molecule IR1061, NO donor BNN6 and β-lapachone (Lapa) were firstly encapsulated in the heat-responsive palmitoyl phosphatidylcholine/cholesterol liposome, followed by fusion with B16F10 cell membrane (CM) to obtain biomimetic CM-Lip@(IR/BNN6/Lapa). The hybrid membrane-based nanodrug displayed excellent biocompatibility and melanoma-targeting efficiency. Upon 1064 nm laser irradiation, the mild photothermal effect of CM-Lip@(IR/BNN6/Lapa) firstly triggered the release of NO and Lapa, which subsequently catalyzed the quinone oxidoreductase 1 (NQO1) overexpressed in tumors to produce O₂^•-, finally caused intraturmal ONOO^- boost via cascade reaction. The boosted ONOO^- could effectively inhibit melanoma by ways of triggering mitochondrion-mediated apoptotic pathway, upregulating 3-nitrotyrosine expression, inducing DNA damage and inhibiting DNA repair enzyme expression of poly (ADP-ribose) polymerase 1 (PARP-1). Moreover, ONOO^- displayed excellent immunoactivation and immunomodulation activities by effectively inducing immunogenic tumor cell death, promoting dendritic cells maturation, increasing cytotoxic T lymphocytes expression and repolarizing M1-phenotype macrophages.

2025-02-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency

Article

作者: Terburgh, Karin ; du Plessis, Charl ; Louw, Roan ; Goolab, Shivani ; Scholefield, Janine

Mitochondrial diseases, often caused by defects in complex I (CI) of the oxidative phosphorylation system, currently lack curative treatments. Human-relevant, high-throughput drug screening platforms are crucial for the discovery of effective therapeutics, with induced pluripotent stem cells (iPSCs) emerging as a valuable technology for this purpose. Here, we present a novel iPSC model of NDUFS4-related CI deficiency that displays a strong metabolic phenotype in the pluripotent state. Human iPSCs were edited using CRISPR-Cas9 to target the NDUFS4 gene, generating isogenic NDUFS4 knockout (KO) cell lines. Sanger sequencing detected heterozygous biallelic deletions, whereas no indel mutations were found in isogenic control cells. Western blotting confirmed the absence of NDUFS4 protein in KO iPSCs and CI enzyme kinetics showed a ~56 % reduction in activity compared to isogenic controls. Comprehensive metabolomic profiling revealed a distinct metabolic phenotype in NDUFS4 KO iPSCs, predominantly associated with an elevated NADH/NAD⁺ ratio, consistent with alterations observed in other models of mitochondrial dysfunction. Additionally, β-lapachone, a recognized NAD⁺ modulator, alleviated reductive stress in KO iPSCs by modifying the redox state in both the cytosol and mitochondria. Although undifferentiated iPSCs cannot fully replicate the complex cellular dynamics of the disease seen in vivo, these findings highlight the utility of iPSCs in providing a relevant metabolic milieu that can facilitate early-stage, high-throughput exploration of therapeutic strategies for mitochondrial dysfunction.

2025-01-01·Journal of Colloid and Interface Science

Triggering multiple modalities of cell death via dual-responsive nanomedicines to address the narrow therapeutic window of β-lapachone

Article

作者: Zhao, Yanjun ; Li, Yaru ; Li, Xin ; Liu, Yancheng ; Li, Yao ; Liu, Fang ; Wang, Zheng

The clinical translation of the anticancer drug β-lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe³⁺ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways (e.g., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP's therapeutic window via controlled cargo release and vehicle sensitization.

100 项与 Beta Lapachone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11948

研发状态

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2期	韩国	Yungjin Pharm. Co., Ltd.	2013-01-01
代谢功能障碍相关的脂肪肝病	临床2期	韩国	Yungjin Pharm. Co., Ltd.	2013-01-01
转移性头颈部鳞状细胞癌	临床2期	美国	-	2006-07-01
平滑肌肉瘤	临床2期	美国	-	2006-02-01
腺癌	临床2期	美国	ArQule, Inc.	2005-01-01
转移性胰腺腺癌	临床2期	美国	ArQule, Inc.	2005-01-01
晚期恶性实体瘤	临床2期	美国	-	2003-09-01
头颈部肿瘤	临床2期	-	Arisyn Therapeutics Inc	-
平滑肌瘤	临床2期	-	Arisyn Therapeutics Inc	-
胰腺癌	临床2期	-	Arisyn Therapeutics Inc	-

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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


ASCO2005 人工标引	临床1期	晚期恶性实体瘤	18	ARQ 501	(範醖簾選窪繭淵鹹壓構) = Up to the 390 mg/m2 dose, ARQ 501 exhibited apparent linear pharmacokinetics, 選簾鑰鑰顧願築簾壓遞 (憲襯築壓願鹽範鹽繭餘 ) 更多	积极	2005-06-01
ARVO2004	N/A	视网膜母细胞瘤	-	Beta-lapachone	鏇餘顧觸積膚鬱齋鏇窪(築壓築艱鏇製衊糧願醖) = 鑰選醖範願夢積簾窪鬱艱鏇糧鏇衊願餘範蓋糧 (艱範構製壓窪壓襯廠繭 ) 更多	-	2004-05-01
ARVO2004	N/A	视网膜母细胞瘤	-	Etoposide	襯積鑰積醖積製範鏇艱(製遞鏇衊壓獵獵艱齋鏇) = 繭築蓋蓋夢蓋膚醖積鑰願範餘獵願簾膚餘簾選 (選餘餘窪鑰顧選範構顧 )	-	2004-05-01