Delving into the Latest Updates on Levobutylphthalide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Dl-3-butylphthalide, Dl-3-n-butylphthalide, L-butylphthalide

+ [4]

Target

KCNK x KEAP1 x Nrf2

Action

inhibitors

Mechanism

KCNK inhibitors(Potassium two pore domain channel subfamily K inhibitors), KEAP1 inhibitors(Kelch-like ECH-associated protein 1 inhibitors), Nrf2 inhibitors(Nuclear factor erythroid 2-related factor 2 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Acute myocardial infarctionAlzheimer Disease

Inactive Indication

Acute Ischemic StrokeMetastatic breast cancerPeripheral Nervous System Diseases+ [1]

Originator Organization

CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.

Active Organization

Wenzhou Medical CollegeXuanwu Hospital Capital Medical University

Inactive Organization

CSPC NBP Pharmaceutical Co., Ltd.

Conjupro Biotherapeutics, Inc.

CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Chemotherapy-related cognitive Impairment (CICI) is a series of neurocognitive deficits experienced during and after cancer chemotherapy. Studies have reported that CICI affects 25% to 75% of survivors and can persist for years after chemotherapy is discontinued, causing more severe progressive manifestations and placing a heavy burden on families and society. Numerous studies have proposed several potential mechanisms and etiologies for CICI, including direct neurotoxicity, disruption of the blood-brain barrier, reduced hippocampal neurogenesis, white matter abnormalities, secondary neuroinflammatory responses, and increased oxidative stress. At present, there is no clear and effective diagnosis and therapy for CICI, and how to diagnose and treat cognitive impairment caused by chemotherapy effectively is still the focus and difficulty.
Based on the previous consensus on the application of dl-3-n-butylphthalide, butylphthalein can play a neuroprotective role by reducing oxidative stress and inflammatory response, inhibiting neuronal apoptosis, improving mitochondrial function and other mechanisms, and significantly improve the performance of the central nervous system caused by cerebral ischemia and vascular dementia. However, the increase of neuroinflammatory response and oxidative stress is precisely one of the potential mechanisms of CICI pathogenesis. Therefore, based on the above findings, this study hypothesized that dl-3-n-butylphthalide would also have considerable efficacy in the treatment of CICI.

Start Date01 Jul 2024

Sponsor / Collaborator

The First Hospital Of China Medical University

NCT05976152

/ RecruitingPhase 3IIT

Effect of Butyphthalide on Cognitive Level Change After Cerebral Vascular Event-a Randomized Control Trial (Be-CLEVER)

Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome characterized by cognitive impairment that occurs after a stroke event and persists for at least 24 weeks. Due to the early recovery of conditions such as delirium and transient cognitive impairment after stroke, the diagnosis of PSCI often requires cognitive assessment at 12 to 24 weeks post-stroke to determine the severity of cognitive impairment. It can be classified according to the severity of cognitive impairment as post-stroke cognitive impairment no dementia (PSCIND) and post-stroke dementia (PSD). Recent large international cohort studies have reported an incidence rate of PSCI ranging from 24% to 53.4%, and patients with PSCI have a significantly higher mortality rate compared to those without cognitive impairment. Guidelines such as American Heart Association/American Society of Anesthesiologists (AHA/ASA) and the Chinese "Expert Consensus on the Management of Post-Stroke Cognitive Impairment" propose integrating cognitive impairment and stroke intervention strategies. Early comprehensive intervention and treatment for high-risk individuals after stroke, aiming to delay or prevent the progression from PSCIND to PSD, are the primary goals in the current treatment of PSCI. However, there is currently a lack of large randomized controlled trials (RCTs) for PSCI, and research is still needed to determine whether cognitive-enhancing drugs can reduce the risk of PSCI occurrence and improve outcomes and prognosis for PSCI patients. A randomized, double-blind, multicenter clinical study involving 281 non-dementia vascular cognitive impairment (VCI) patients showed that the overall cognitive scores of patients treated with donepezil for 24 weeks significantly improved compared to the placebo group.
The aim of this study is to evaluate the effectiveness of donepezil in the treatment of post-stroke cognitive impairment. It will be a multicenter, randomized, double-blind, placebo-controlled trial with a 48-week treatment duration. The study will observe the difference in PSCI incidence rate between the donepezil treatment group and the conventional stroke treatment group at 24 weeks and evaluate the improvement in post-stroke cognitive impairment after 6 months of donepezil treatment compared to conventional treatment.
This study will be conducted in two stages: the first stage (0-24 weeks) aims to assess whether donepezil can reduce the risk of PSCI occurrence and will be a multicenter, randomized, double-blind, placebo-controlled study. The second stage (24-48 weeks) aims to evaluate whether donepezil can improve the prognosis of PSCI patients and will also be a multicenter, randomized, double-blind, placebo-controlled study.

Start Date01 Apr 2024

Sponsor / Collaborator

Fudan University

NCT04675450

/ WithdrawnPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of n-Butylphthalide (NBP) Softgel Capsules Administered to Patients With Metastatic Breast Cancer to Prevent Nab-paclitaxel Induced Toxic Neuropathy

Phase 2, randomized, double-blind, Placebo-Controlled, Multiple Dose Study for the treatment of Patients with Metastatic Breast Cancer.

Start Date30 Jun 2023

Sponsor / Collaborator

Conjupro Biotherapeutics, Inc.

[+1]

100 Clinical Results associated with Levobutylphthalide

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100 Translational Medicine associated with Levobutylphthalide

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100 Patents (Medical) associated with Levobutylphthalide

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623

Literatures (Medical) associated with Levobutylphthalide

01 Sep 2025·JOURNAL OF CONTROLLED RELEASE

Dual-barrier traversing liposomes with ROS-responsive rigidity tuning for oral ischemic stroke therapy

Article

Author: Yang, Weijing ; Zhang, Jieke ; Zhang, Shuo ; Lv, Lulu ; Sun, Bingxin ; Yang, Wenhui ; Guo, Jun ; Zhang, Jinjie ; Li, Jianbo

For sustained ischemic stroke intervention, oral delivery remains optimal. However, conventional nanocarriers like liposomes fail to overcome both the intestinal epithelial (IEB) and blood-brain barriers (BBB). We engineered dual-functional, butylphthalide (NBP)-loaded liposomes (C-NBP Lip) via amphiphilic cytidine-lipoic acid conjugate (LA-C) functionalization, establishing the first unified nanoplatform for nucleoside transporter-mediated targeting and reactive oxygen species (ROS)-responsive membrane modulation. Our strategy exploits cytidine's dual affinity for apical concentrative (CNT1) and basolateral equilibrative (ENT1) nucleoside transporters on gut epithelia, enabling efficient intestinal translocation and subsequent ENT1-mediated BBB transcytosis via a single ligand. Crucially, hydrophobic interactions between LA-C's dithiolane ring and phospholipids dynamically tuned membrane rigidity of C-NBP Lip. enabling ROS-triggered drug release at ischemic lesions. In rats, C-NBP Lip exhibited 44.61 % oral bioavailability, 137 % higher than free NBP (18.80 %), and demonstrated robust neuroprotection without toxicity in both short- and long-term rat ischemic stroke model. This work pioneers "barrier-adaptive liposomes" that integrate endogenous transporter exploitation with stimulus-responsive membrane engineering for transformative oral brain delivery.

01 Sep 2025·TOXICOLOGY AND APPLIED PHARMACOLOGY

Dl-3-n-butylphthalide attenuates acute myocardial infarction by inhibiting the binding of Nrf2/Keap1

Article

Author: Gao, Haocheng ; Chen, Kaifeng ; Huang, Zhiqiang ; Huang, Fulai ; Zhao, Shengnan ; Chen, Gaozhi ; Xu, Guolyu ; Fu, Lili ; Yan, Yixiao ; Mou, Lingyi ; Cheng, Linting

Acute myocardial infarction (AMI) is a prevalent cardiovascular condition often encountered in clinics. It is characterized by an imbalance in the myocardial oxygen supply and demand and is thought to be associated to cell apoptosis and oxidative stress. Dl-3-n-butylphthalide (NBP), a natural product extracted from celery for the clinical treatment of ischemic stroke, may mitigate the effects of myocardial infarction. To test this hypothesis, isoproterenol (ISO) which is a β-adrenoceptor agonist, was used to simulate the metabolic and morphological abnormalities of AMI. The results demonstrated that NBP significantly alleviated ISO-induced cardiac dysfunction, showing beneficial effects on cardiac inflammation, apoptosis, fibrosis, and mitochondrial damage. Western blotting (WB), and qRT-PCR suggest that NBP may regulate the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further experiments revealed that NBP blocks the binding of Kelch-like ECH-associated protein-1 (Keap1) and Nrf2 and then inhibits the ubiquitination degradation of Nrf2. This study identifies NBP as a potent therapeutic agent for ISO-induced cardiac dysfunction by inhibiting Nrf2-Keap1 binding.

01 Aug 2025·MOLECULAR NEUROBIOLOGY

Dl-3-n-Butylphthalide Promotes Neurogenesis in Ischemic Stroke Mice Through Wnt/β-Catenin Signaling Activation and Neurotrophic Factor Production

Article

Author: Zhang, Lan ; Shang, Wenyan ; Xu, Renhao ; Zhang, Xiangjian ; Zhang, Jian ; Liu, Ying ; Chen, Rong ; Gao, Xuan ; Zhang, Cong ; Du, Yuanyuan

Synchronized neurogenesis and angiogenesis after stroke have been well documented, and inducing neurovascular remodeling may provide a promising strategy to promote tissue repair and functional recovery. Dl-3-n-Butylphthalide (NBP) was reported to exert a potent angiogenic activity in rodent models of stroke. However, little is currently known regarding the effects and mechanisms of NBP on neurogenesis in ischemic stroke. This study aimed to determine whether and how NBP promotes neurogenesis in cerebral ischemic injury. Adult C57BL/6 mice, subjected to distal middle cerebral artery occlusion (dMCAO), were treated with NBP. The efficacy of NBP was assessed using neurologic deficits and infarct volume. Immunofluorescent staining was applied to evaluate neurogenesis. The regulation of the Wnt/β-catenin signaling pathway and the expression of neurotrophic factors were detected by western blotting and qRT-PCR. Administration of NBP reduced infarct volume and ameliorated neurological deficits after stroke. NBP promoted the proliferation of NSCs in the SVZ, migration of neuroblasts along the corpus callosum, and differentiation of neuroblasts toward neurons in the peri-infarct zone, resulting in restored neural function. Moreover, we revealed that NBP-induced neurogenesis was associated with the activation of the Wnt/β-catenin pathway, which was reversed by DKK1. In addition, NBP increased the production of VEGF and BDNF. Our data have unveiled the potentials of NBP to promote neurogenesis and neural functional recovery after stroke, depending on Wnt/β-catenin signaling activation and neurotrophic factor production. Thus, NBP may be a promising candidate for delayed treatment of ischemic stroke.

100 Deals associated with Levobutylphthalide

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Phase 2	-	Conjupro Biotherapeutics, Inc.	30 Jun 2023
Metastatic breast cancer	Phase 2	-	CSPC NBP Pharmaceutical Co., Ltd.	30 Jun 2023
Peripheral Nervous System Diseases	Phase 2	-	CSPC NBP Pharmaceutical Co., Ltd.	30 Jun 2023
Peripheral Nervous System Diseases	Phase 2	-	Conjupro Biotherapeutics, Inc.	30 Jun 2023
Acute Ischemic Stroke	Phase 2	United States	CSPC NBP Pharmaceutical Co., Ltd.	28 Feb 2018
Stroke	IND Application	China	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	17 Feb 2005
Acute myocardial infarction	Preclinical	China	Wenzhou Medical College	01 Sep 2025
Alzheimer Disease	Preclinical	China	Xuanwu Hospital Capital Medical University	16 Jun 2023

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed Manual	Not Applicable	Aphasia	118	DL-3-N-butylphthalide (NBP) soft capsules	kidszcwbfv(cvinflnlcb): Difference (Mean) = 0.106 (95% CI, 0.018 - 0.195), P-Value = 0.003 View more	Positive	22 Nov 2024
				Placebo
AAIC2019	Not Applicable	Alzheimer Disease	35	Combination therapy group (NBP 200mg three times daily plus donepezil 5mg or 10mg daily)	laexrfpahz(vumyokgviu): OR = 0.866 (95% CI, 0.082 - 9.179), P-Value = 0.905	Positive	01 Jul 2019
				Monotherapy group (donepezil 5mg or 10mg daily)
NCT02149875 (CTgov)	Phase 1/2	Acute Ischemic Stroke	84	Dl-3-n-butylphthalide (Dl-3-n-butylphthalide)	kpztpkttvc(mthfzokonw) = uahmjselvd dlxtwexjjx (exvxswnmbx, 2.48) View more	-	18 May 2016
				Cerebrolysin (Cerebrolysin)	kpztpkttvc(mthfzokonw) = aoatclsjrs dlxtwexjjx (exvxswnmbx, 5.81) View more