Last update 01 Nov 2024

LY96

Last update 01 Nov 2024

Basic Info

Synonyms

ESOP-1, ESOP1, Ly-96

+ [5]

Introduction

Binds bacterial lipopolysaccharide (LPS) (PubMed:17803912, PubMed:17569869). Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria (PubMed:11160242, PubMed:11593030). Enhances TLR4-dependent activation of NF-kappa-B (PubMed:10359581). Cells expressing both LY96 and TLR4, but not TLR4 alone, respond to LPS (PubMed:10359581).

Drugs associated with LY96

ACT-001(Accendatech)

Target

LY96 x TLR4

Mechanism

LY96 inhibitors [+1]

Active Org.

Accendatech Co. Ltd. [+3]

Originator Org.

Accendatech Co. Ltd.

Active Indication

Diffuse Intrinsic Pontine Glioma [+10]

Inactive Indication

Neuromyelitis Optica [+1]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LK2(6)A(L)

Target

LY96

Mechanism

LY96 inhibitors

Active Org.

Liaoning Normal University

Originator Org.

Liaoning Normal University

Active Indication

Acute Lung Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

IS-7

Target

LY96

Mechanism

LY96 inhibitors

Active Org.

Liaoning Normal University

Originator Org.

Liaoning Normal University

Active Indication

Acute Lung Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with LY96

CTR20232173 / RecruitingPhase 2

一项单臂、多中心评价ACT001联合放疗治疗初诊弥漫内生型桥脑胶质瘤患者安全性和有效性的II期临床研究

[Translation] A single-arm, multicenter Phase II clinical study evaluating the safety and efficacy of ACT001 combined with radiotherapy in patients with newly diagnosed diffuse intrinsic pontine glioma

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 LY96

100 Translational Medicine associated with LY96

0 Patents (Medical) associated with LY96

1,614

Literatures (Medical) associated with LY96

01 Dec 2024·European Journal of Medicinal Chemistry

Discovery of pyrazolo[1,5-a]pyrimidine derivatives targeting TLR4−TLR4∗ homodimerization via AI-powered next-generation screening

Article

Author: Fang, Xiao-Min ; Zhang, Shan-Zhuo ; Wang, Meng ; Diao, Wei-Ming ; Yan, Shuai-Ting ; Li, Jun ; Yin, Hang ; Jiang, Yao-Yao

TLR4 signaling is instrumental in orchestrating multiple aspects of innate immunity. Developing small molecule inhibitors targeting the TLR4 pathway holds potential therapeutic promise for TLR4-related disorders. Herein, an artiﬁcial intelligence (AI)-powered next-generation screening approach, employing HelixVS and HelixDock, was utilized to focus on the TLR4-TLR4∗ (a second copy of TLR4) homodimerization surface, leading to the identification of a potent pyrazolo[1,5-a]pyrimidine derivative, designated as compound 1. An extensive structure-activity relationship (SAR) exploration culminated in the discovery of the lead compound TH023, which effectively blocked the LPS-stimulated NF-κB activation and nitric oxide overproduction in HEK-Blue hTLR4 and RAW264.7 cells, with IC₅₀ values of 0.354 and 1.61 μM, respectively. Molecular dynamic (MD) simulations indicated that TH023 stabilized TLR4-MD-2 and disrupted its association with TLR4∗. Moreover, TH023 alleviated the lung injury and decreased pro-inflammatory cytokine levels in LPS-induced septic mice. These findings not only illuminated the strategic advantage of HelixDock in advancing the frontiers of AI-driven drug discovery, but also provided valuable structural insights for the rational design of TLR4-TLR4∗ protein-protein interaction (PPI) inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold. Overall, this study validated a new strategy for TLR4 signaling regulation by targeting its dimerization, thereby underscoring the therapeutic promise of TH023 in treating TLR4-mediated inflammatory diseases.

01 Dec 2024·International Immunopharmacology

Dried tangerine peel polysaccharide accelerates wound healing by recruiting anti-inflammatory macrophages

Article

Author: Guo, Suqin ; Lin, Jiayin ; Feng, Yanxian ; Tang, Fuqiang ; Li, Wenxi ; Wang, Lingzhi ; Gong, Huafang ; Xu, Jucai ; Li, Yinggang ; Li, Wu ; Liu, Hui ; Jiang, Xin

Macrophage polarization is a key process involved in wound healing. The continuous release of proinflammatory cytokines by macrophages inhibits the healing process of chronic wounds, such as diabetic wounds. To promote wound healing, it is important to change the phenotype of resident macrophages to prevent inflammation. We previously reported that dried tangerine peel polysaccharide (DTPP) binds to and inhibits the TLR4/MD-2 complex, which is crucial for the inflammatory activation of macrophages, suggesting the potential of DTPP in wound healing applications. Both zebrafish and mouse models were used to evaluate the therapeutic efficacy of DTPP. Moreover, we found that DTPP recruited macrophages to the wound area and promoted their M2 repolarization. Using hyperglycaemic zebrafish and db/db mouse models, we discovered that DTPP accelerated wound healing in vivo in metabolic disorders. Our results suggest that DTPP promotes the recruitment of macrophages, shifts macrophages towards the anti-inflammatory M2 phenotype, and ultimately accelerates the wound healing process.

01 Dec 2024·Fitoterapia

Three undescribed isosteroidal alkaloids from the bulbs of Fritillaria ussuriensis maxim: Anti-inflammatory activities, docking studies and molecular dynamic

Article

Author: Jiang, Peng ; Chen, Qing-Shan ; Yang, Bing-You ; Zhang, Li-Li ; Lu, Dong-Xv ; Li, Yan-Ying ; Guan, Wei ; Luo, Yu-Meng ; Pan, Juan ; Hao, Zhi-Chao ; Zhang, Yi-Qiang ; Liu, Yan ; Zhuang, Lei-Xin ; Kuang, Hai-Xue

Three undescribed isosteroidal alkaloids (1-3), along with two known ones (4, 5) were isolated from the bulbs of Fritillaria ussuriensis Maxim, their structures were established by comprehensive analyses of the 1D, 2D-NMR and HR-ESI-MS data. Meanwhile, LPS-activated RAW 264.7 macrophages were used to determine the potential anti-inflammatory activity of all the alkaloids in vitro. Among them, compounds 1 and 4 showed significant inhibitory effects against LPS-induced NO production with IC₅₀ values of 7.79 μM and 11.22 μM, respectively. Compounds 1 and 4 were performed between molecular docking with TLR4/MD2. Based on the results of cell experiments and binding affinities, compound 1 (UG) was chosen for molecular dynamic analysis together with the TLR4/MD2 protein.

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LY96

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