Delving into the Latest Updates on Beta Lapachone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [6]

Target

NQO1

Action

inhibitors

Mechanism

NQO1 inhibitors(Quinone reductase 1 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

AdenocarcinomaAdvanced Malignant Solid NeoplasmFibrosis+ [9]

Originator Organization

Arisyn Therapeutics Inc

Active Organization-

Inactive Organization

Yungjin Pharm. Co., Ltd.

ArQule, Inc.Arisyn Therapeutics Inc

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC15H14O3

InChIKeyQZPQTZZNNJUOLS-UHFFFAOYSA-N

CAS Registry4707-32-8

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.

01 May 2025·Chinese Chemical Letters

A β-lapachone-loaded iron-polyphenol nanocomplex enhances chemodynamic therapy through cascade amplification of ROS in tumor

Author: Xu, Xiaodan ; Tang, Jianbin ; Xiao, Bing ; Hu, Hongjie ; Xu, Hongxia ; Shi, Xueying ; Zhang, Wei ; Zhou, Zhuxian ; Shen, Youqing ; Shao, Shiqun ; Zhou, Xiaoxuan

Chemodynamic therapy (CDT), using Fenton agents to generate highly cytotoxic .OH from H2O2 has been demonstrated as a powerful anticancer method.However, the insufficient endogenous H2O2 in tumor cells greatly limited its therapeutic effect.Herein, we prepared a pH-responsive β-lapachone-loaded iron-polyphenol nanocomplex (LIPN) through a one-pot method. β-Lapachone in LIPN selectively enhanced H2O2 concentration in tumor cells, and ferrous ions cascadely generated abundant cytotoxic .OH.Therefore, LIPN with cascade amplification of reactive oxygen species (ROS) showed high chemodynamic cytotoxicity in tumor cells, efficiently improving the expression of damage-associated mol. patterns (DAMPs), and exerting strong immunogenic cell death (ICD).As a result, LIPN exhibited efficient tumor inhibition ability in 4T1 s.c. tumor model in vivo with great biocompatibility.Addnl., the infiltration of cytotoxic CD8+ T lymphocytes and inhibition of regulatory CD4+ FoxP3+ T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore, this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.

01 May 2025·Cell Biology International

Chlorogenic Acid Enhances Beta‐Lapachone‐Induced Cell Death by Suppressing Autophagy in NQO1‐Positive Cancer Cells

Article

Author: Bahar, Md Entaz ; Zada, Sahib ; Kim, Wanil ; Kim, Deok Ryong

ABSTRACTResistance to apoptosis‐inducing drugs frequently occurs in cancer cells, limiting their usefulness in ongoing cancer treatment. Despite ongoing efforts to overcome drug resistance, a definitive solution remains elusive. However, autophagy inhibition has been shown to enhance the effectiveness of some anticancer drugs and is a possible strategy for overcoming drug resistance. In this study, we demonstrate that chlorogenic acid (CGA), a natural antioxidant, significantly enhances beta‐lapachone (β‐Lap)‐induced cell death in cancer cells. The augmented apoptosis induced by CGA is associated with activation of protein kinase A (PKA) in β‐Lap–treated cells, independent of the antioxidant properties of CGA. As a result, PKA activation in cancer cells co‐treated with β‐Lap and CGA effectively inhibits autophagy. Notably, PKA activation leads to phosphorylation of microtubule‐associated protein 1 A/1B‐light chain 3 (LC3) at the serine 12 residue, causing autophagy suppression irrespective of mTORC activity. Importantly, the cell death induced by β‐Lap and CGA in NQO1‐overexpressing breast or lung cancers is closely linked to autophagy inhibition. These findings suggest that combining β‐Lap and CGA might be a novel strategy for cancer therapy, particularly for overcoming drug resistance caused by autophagy induction in cancer cells.

100 Deals associated with Beta Lapachone

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11948

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 2	United States	Yungjin Pharm. Co., Ltd.	01 Jan 2013
Metabolic dysfunction-associated steatotic liver disease	Phase 2	United States	Yungjin Pharm. Co., Ltd.	01 Jan 2013
Squamous cell carcinoma of head and neck metastatic	Phase 2	United States	-	01 Jul 2006
Leiomyosarcoma	Phase 2	United States	-	01 Feb 2006
Adenocarcinoma	Phase 2	United States	ArQule, Inc.	01 Jan 2005
Pancreatic adenocarcinoma metastatic	Phase 2	United States	ArQule, Inc.	01 Jan 2005
Advanced Malignant Solid Neoplasm	Phase 2	United States	-	01 Sep 2003
Head and Neck Neoplasms	Phase 2	-	Arisyn Therapeutics Inc	-
Leiomyoma	Phase 2	-	Arisyn Therapeutics Inc	-
Pancreatic Cancer	Phase 2	-	Arisyn Therapeutics Inc	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2005 Manual	Phase 1	Advanced Malignant Solid Neoplasm	18	ARQ 501	(xgimxqlxae) = Up to the 390 mg/m2 dose, ARQ 501 exhibited apparent linear pharmacokinetics, mknngqxpyd (icugpbxyal ) View more	Positive	01 Jun 2005
ARVO2004	Not Applicable	Retinoblastoma	-	Beta-lapachone	gnyyhiiudh(ijdgmivwmp) = qgqeyvcgju scjqrnpmqu (eimhxtqziy ) View more	-	01 May 2004
ARVO2004	Not Applicable	Retinoblastoma	-	Etoposide	bwyujxgioa(jwxoxutkah) = omddclubwr zgqxwtoxjw (dcisvcqvke )	-	01 May 2004