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+ [10]

原研机构

Arisyn Therapeutics Inc

在研机构-

非在研机构

Arisyn Therapeutics Inc

Yungjin Pharm. Co., Ltd.F. Hoffmann-La Roche Ltd.

+ [1]

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

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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909

项与 Beta Lapachone 相关的文献（医药）

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.

2024-12-31·OncoImmunology

β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers

Article

作者: Zhao, Ye ; Huang, Xiumei ; Fu, Yang-Xin ; Jiang, Shu ; Li, Xiaoguang ; Chen, Yaomin ; Chen, Xiang ; Tumbath, Soumya ; Zhou, Hao ; Jiang, Lingxiang ; Yin, Zhijun ; Lu, Tao ; Zhang, Taolan ; Zahid, Kashif Rafiq

NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. β-Lapachone (β-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between β-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that β-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with β-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug's therapeutic efficacy. Further, the presence of β-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8⁺ T cell proliferation. β-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-β expression and reduced TGF-β cytokine expression, along with increased CD95 and CD54 surface markers. β-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into β-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by β-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the β-Lap-induced antitumor activity against NQO1-positive murine tumors.

2024-12-01·Computational and Structural Biotechnology Journal

Discovering novel Cathepsin L inhibitors from natural products using artificial intelligence

Article

作者: Wang, Hao ; Li, Qi ; Zhou, Si-Rui ; Zhu, Juan-Juan ; Kim, Hanna ; Yang, Jin-Kui

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited. In this study, we used a combination of artificial intelligence and experimental methods to identify new CTSL inhibitors from natural products. Through a robust deep learning model and molecular docking, we screened 150 molecules from natural products for experimental validation. At a concentration of 100 µM, we found that 36 of them exhibited more than 50 % inhibition of CTSL. Notably, 13 molecules displayed over 90 % inhibition and exhibiting concentration-dependent effects. The molecular dynamics simulation on the two most potent inhibitors, Plumbagin and Beta-Lapachone, demonstrated stable interaction at the CTSL active site. Enzyme kinetics studies have shown that these inhibitors exert an uncompetitive inhibitory effect on CTSL. In conclusion, our research identifies Plumbagin and Beta-Lapachone as potential CTSL inhibitors, offering promising candidates for the treatment of metabolic disorders and illustrating the effectiveness of artificial intelligence in drug discovery.

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
转移性胰腺腺癌	临床2期	美国	ArQule, Inc.	2005-01-01
头颈部肿瘤	临床2期	-	Arisyn Therapeutics Inc	-
头颈部肿瘤	临床2期	-	Arisyn Therapeutics Inc	-
头颈部肿瘤	临床2期	-	F. Hoffmann-La Roche Ltd.	-
头颈部肿瘤	临床2期	-	F. Hoffmann-La Roche Ltd.	-
平滑肌瘤	临床2期	-	F. Hoffmann-La Roche Ltd.	-
平滑肌瘤	临床2期	-	Arisyn Therapeutics Inc	-
平滑肌瘤	临床2期	-	ArQule, Inc.	-
胰腺癌	临床2期	-	F. Hoffmann-La Roche Ltd.	-
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	(鏇餘觸網鬱鏇餘製壓鹽) = Up to the 390 mg/m2 dose, ARQ 501 exhibited apparent linear pharmacokinetics, 衊淵餘製膚繭憲範夢襯 (糧鹽餘網鏇壓襯顧蓋糧 ) 更多	积极	2005-06-01
ARVO2004	N/A	视网膜母细胞瘤	-	Beta-lapachone	鹽獵積遞積選壓鬱鏇遞(鏇簾鏇鹹鏇夢遞窪築鏇) = 顧餘糧糧構鑰糧鏇網餘鹹鏇顧糧夢製壓蓋製憲 (鑰鹹顧築淵選齋壓膚壓 ) 更多	-	2004-05-01
ARVO2004	N/A	视网膜母细胞瘤	-	Etoposide	齋鹽顧鏇繭製遞獵獵糧(齋簾鑰衊製構醖築鑰艱) = 壓選餘鏇觸蓋醖壓膚鹽選餘構憲廠憲餘製獵製 (遞醖壓窪襯窪糧鏇範鏇 )	-	2004-05-01