Delving into the Latest Updates on ACT-001(Accendatech) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

dimethylaminomicheliolide Fumarate

Target

LY96 x TLR4

Mechanism

LY96 inhibitors(lymphocyte antigen 96 inhibitors), TLR4 antagonists(Toll like receptor 4 antagonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesRespiratory Diseases+ [6]

Active Indication

Diffuse Intrinsic Pontine GliomaNon-Small Cell Lung CancerSmall Cell Lung Cancer+ [9]

Inactive Indication

Recurrent Glioblastoma

Originator Organization

Accendatech Co. Ltd.

Active Organization

Accendatech Co. Ltd.Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.Accendatech AU Pty Ltd.

+ [1]

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationSpecial Review Project (CN), Rare Pediatric Disease (US), Fast Track (US), Orphan Drug (EU)

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Structure/Sequence

Molecular FormulaC21H31NO7

InChIKeyPDWGVXJIDIRQME-DCNFBYMVSA-N

CAS Registry1582289-91-5

View All Structures (2)

主要目的：评估ACT001联合放疗治疗初诊DIPG受试者的肿瘤缓解情况和安全性（疗效探索期）、验证ACT001联合放疗对初诊DIPG受试者的肿瘤缓解情况和总生存时间的影响（疗效验证期）；次要目的：初诊DIPG受试者对ACT001联合放疗的疗效（疗效探索期）、验证ACT001联合放疗对初诊DIPG受试者的其他疗效验证ACT001联合放疗对初诊DIPG受试者的安全性（疗效验证期）；探索性目的：评估治疗对生物标志物的影响及其与疗效之间的关系、基于PopPK分析方法，表征ACT001及代谢产物的PK特征、探索ACT001的暴露与效应之间的关系

[Translation]

Primary objectives: To evaluate the tumor remission and safety of ACT001 combined with radiotherapy in newly diagnosed DIPG subjects (efficacy exploration phase), and to verify the effect of ACT001 combined with radiotherapy on tumor remission and overall survival time in newly diagnosed DIPG subjects (efficacy verification phase); Secondary objectives: To evaluate the efficacy of ACT001 combined with radiotherapy in newly diagnosed DIPG subjects (efficacy exploration phase), to verify other efficacy of ACT001 combined with radiotherapy in newly diagnosed DIPG subjects, and to verify the safety of ACT001 combined with radiotherapy in newly diagnosed DIPG subjects (efficacy verification phase); Exploratory objectives: To evaluate the impact of treatment on biomarkers and its relationship with efficacy, to characterize the PK characteristics of ACT001 and metabolites based on PopPK analysis methods, and to explore the relationship between exposure and effect of ACT001

Start Date30 Aug 2023

Sponsor / Collaborator

Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.

ChiCTR2300074598

/ SuspendedPhase 2IIT

A single arm, multicenter evaluation of the safety and efficacy of ACT001 combined with radiotherapy in the newly diagnosed diffuse intrinsic pontine gliomas Phase II Clinical Study

Start Date15 Aug 2023

Sponsor / Collaborator-

CTR20230452

/ RecruitingPhase 2

一项随机、盲法、安慰剂对照的评价ACT001增强肺癌脑转移放疗疗效和减轻全脑放疗毒副反应的IIb/III期临床研究

[Translation] A randomized, blinded, placebo-controlled Phase IIb/III clinical study to evaluate the efficacy of ACT001 in enhancing radiotherapy for brain metastases of lung cancer and reducing the toxicity and side effects of whole-brain radiotherapy

主要目的：评估ACT001联合全脑放疗对肺癌脑转移患者颅内肿瘤的疗效。次要目的：以其他疗效终点评估ACT001联合全脑放疗对肺癌脑转移患者颅内外肿瘤的疗效；评估ACT001降低全脑放疗毒副反应的作用；评估ACT001对肺癌脑转移患者生活质量的影响；评价ACT001在受试人群中的药代动力学（PK）特征。探索性目的：评估ACT001联合全脑放疗治疗肺癌脑转移患者颅内外肿瘤的疗效；基于群体药代动力学（PopPK）分析方法，表征ACT001的PK特征；评估治疗血液生物标志物的变化及其与疗效之间的关系；探索ACT001的暴露与效应之间的关系。

[Translation]

Primary objective: To evaluate the efficacy of ACT001 combined with whole brain radiotherapy for intracranial tumors in patients with brain metastases from lung cancer. Secondary objectives: To evaluate the efficacy of ACT001 combined with whole brain radiotherapy for intracranial and extracranial tumors in patients with brain metastases from lung cancer using other efficacy endpoints; To evaluate the effect of ACT001 in reducing the toxic and side effects of whole brain radiotherapy; To evaluate the effect of ACT001 on the quality of life of patients with brain metastases from lung cancer; To evaluate the pharmacokinetic (PK) characteristics of ACT001 in the study population. Exploratory objectives: To evaluate the efficacy of ACT001 combined with whole brain radiotherapy in the treatment of intracranial and extracranial tumors in patients with brain metastases from lung cancer; To characterize the PK characteristics of ACT001 based on the population pharmacokinetic (PopPK) analysis method; To evaluate the changes in therapeutic blood biomarkers and their relationship with efficacy; To explore the relationship between exposure and effect of ACT001.

Start Date05 Apr 2023

Sponsor / Collaborator

Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.

100 Clinical Results associated with ACT-001(Accendatech)

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100 Translational Medicine associated with ACT-001(Accendatech)

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100 Patents (Medical) associated with ACT-001(Accendatech)

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49

Literatures (Medical) associated with ACT-001(Accendatech)

01 Nov 2024·Cell Proliferation

MCL restrained ROS/AKT/ASAH1 pathway to therapy tamoxifen resistance breast cancer by stabilizing NRF2

Article

Author: Shao, Di ; Han, Xiao ; Zhang, Yupeng ; Li, Chenggang ; Lin, Zhoujun ; Fu, Zhenkun ; Wang, Changjun ; Zhang, Shengjie ; Li, Yin

AbstractTamoxifen resistance is a common and difficult problem in the clinical treatment of breast cancer (BC). As a novel antitumor agent, Micheliolide (MCL) has shown a better therapeutic effect on tumours; however, little is known about MCL and its role in BC therapy. With tamoxifen stimulation, drug‐resistant BC cells MCF7TAMR and T47DTAMR obtained a high oxidative status and Amidohydrolase 1 (ASAH1) was abnormally activated. The inhibition of ASAH1 rescued the sensitivity of resistant cells to tamoxifen. We found that MCL inhibited the expression of ASAH1 and cell proliferation, especially in MCF7TAMR and T47DTAMR cells. The high oxidative stress status of resistant cells stimulated the expression of ASAH1 by positively regulating AKT, which was restrained by MCL. MCL activated NRF2 by directly binding to KEAP1 and promoting the antioxidant level of tamoxifen‐resistant (TAMR) cells. In addition, ACT001, the prodrug of MCL, significantly inhibited the tumour growth of TAMR cells in preclinical xenograft tumour models. In conclusion, ASAH1 mediates tamoxifen resistance in ER‐positive BC cells. MCL could activate the cellular antioxidant system via NRF2/KEAP1 and inhibit ASAH1 expression through the ROS/AKT signalling pathway, thus suppressing cell proliferation. MCL could be used as a potential treatment for TAMR‐BC.

01 Sep 2024·Biomedicine & Pharmacotherapy

ACT001 inhibits primary central nervous system lymphoma tumor growth by enhancing the anti-tumor effect of T cells

Article

Author: Liu, Zhaoyun ; Fu, Rong ; Song, Jia ; Wang, Guanrou ; Ding, Kai ; Liu, Hui

Primary central nervous system lymphoma (PCNSL) is a group of malignant brain tumors with a poor prognosis, and new therapeutic approaches for this tumor urgently need to be investigated. Formulated from a long-standing anti-inflammatory drugs, ACT001 has demonstrated in clinical research to be able to pass through the blood-brain barrier (BBB) and affect the central nervous system. The effects of ACT001 on PCNSL cell apoptosis, proliferation and immune-related indexes were detected by flow cytometry, and the efficacy of ACT001 was verified in vivo by constructing a mouse PCNSL tumor model. ACT001 significantly inhibited PCNSL cell proliferation and induced apoptosis in vitro. In addition, ACT001 can significantly inhibit the PD-1/PD-L1 expression and restore the function of T cells, so that the immune system cannot allow tumor cells to escape. In vivo experiments show that co-infusion of ACT001 and T cells effectively inhibits PCNSL tumor growth in NSG mice. Our work describes the inhibitory effect of ACT001 on the PCNSL cell line and demonstrated the inhibitory effect of ACT001 on immune checkpoints.

01 May 2024·European Journal of Pharmacology

Alleviative effects of the parthenolide derivative ACT001 on insulin resistance induced by sodium propionate combined with a high-fat diet and its potential mechanisms

Article

Author: Zuo, Xiang ; Bai, Huijuan ; Zhao, Xin ; Zhang, Shuhui ; Feng, Xizeng ; Zhao, Qili ; Luan, Jialu ; Yu, Qian

The increasing side effects of traditional medications used to treat type II diabetes have made research into the development of safer and more effective natural medications necessary. ACT001, a derivative of parthenolide, has been shown to have good anti-inflammatory and antitumor effects; however, its role in diabetes is unclear. The short-chain fatty acid propionate is a common food preservative that has been found to cause disturbances in glucose metabolism in mice and humans. This study aimed to investigate whether sodium propionate could aggravate insulin resistance in obese mice and cause diabetes and to study the alleviative effects and potential mechanisms of action of ACT001 on insulin resistance in diabetic mice. Type II diabetic mice were adminietered sodium propionate combined with a high-fat diet (HFD + propionate) by gavage daily for four weeks. Biochemical analysis showed that ACT001 significantly affected blood glucose concentration in diabetic mice, mainly by downregulating the expression of phosphoenolpyruvate carboxykinase 2 and glucose-6-phosphatase. Meanwhile, the level of fatty acid-binding protein 4 in the liver was significantly decreased. ACT001 has a protective effect on the liver and adipose tissue of mice. In addition, the results of the running wheel experiment indicated that ACT001 alleviated the circadian rhythm disorder caused by insulin resistance to a certain extent. This study revealed the potential mechanism by which ACT001 alleviates insulin resistance and provides ideas for developing natural antidiabetic drugs.

100 Deals associated with ACT-001(Accendatech)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	05 Apr 2023
Small Cell Lung Cancer	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	05 Apr 2023
Breast Cancer	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	16 Feb 2021
Hepatocellular Carcinoma	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	16 Feb 2021
Melanoma	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	16 Feb 2021
Advanced Malignant Solid Neoplasm	Phase 2	CN	Tianjin Xinyi Shangde Biomedical Technology Co., Ltd.	10 Sep 2020
Progressive fibrotic interstitial lung disease	Phase 2	AU	Accendatech AU Pty Ltd.	29 Jul 2020
Glioblastoma	Phase 2	CN	Accendatech Co. Ltd.	30 Jun 2020
Neuromyelitis Optica	Phase 2	CN	Accendatech Co. Ltd.	14 May 2020
Recurrent Glioblastoma	Phase 1	US	Accendatech Co. Ltd.	22 Sep 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ACT001 (EHA2024)	Not Applicable	Primary Central Nervous System Lymphoma	-	ACT001	vtmgnkbslk(duiiqxppmg) = yjjbsnbccu ledmeesaqr (bzjohizfif )	Positive	14 May 2024