Delving into the Latest Updates on GL-V9 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

AMPK

Action

agonists

Mechanism

AMPK agonists(AMP活化蛋白激酶激动剂)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [2]

Active Indication

Acute Myeloid LeukemiaFibrosis, LiverLymphoid neoplasm

Inactive Indication-

Originator Organization

China Pharmaceutical University

Active Organization

Southeast University

China Pharmaceutical University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Liver fibrosis is an inevitable outcome of various manifestations of progressive chronic liver disease. Clinical evidence suggests that gut microbiota contributes to the progression of liver fibrosis via gut-liver axis. Our previous research demonstrated that GL-V9, one of flavonoids compounds, is effective in alleviating liver fibrosis in mice. Based on that, we decided to delve into the alterations in gut microbiota profiling of GL-V9-treated mice with liver fibrosis and identify the bacterial species exhibiting anti-fibrotic potential.

METHODS:

We explored gut microbial profile of GL-V9-treated mice with liver fibrosis via 16S rRNA gene sequencing. Mouse models of liver fibrosis were established and treated accordingly. Then, indexes of liver fibrosis and inflammation were measured by sections staining, biochemical detection and RT-qPCR. Regulatory T (Treg) cells infiltration was detected by flow cytometry. Furthermore, we detected short-chain fatty acids (SCFAs) content by GC-MS and explored the role of SCFAs in liver fibrosis.

RESULTS:

Firstly, Bacteroides acidifaciens were screened out by 16S rRNA gene sequencing based on GL-V9 treatment. Oral administration of Bacteroides acidifaciens attenuated CCl₄-induced liver fibrosis effectively, reduced the expressions of pro-inflammatory factor and suppressed the infiltration of Treg cells. Additionally, SCFAs, the main metabolites of Bacteroides acidifaciens, were further demonstrated the suppression of fibrosis and inflammation. Mechanistically, Bacteroides acidifaciens regulated SCFAs metabolic homeostasis and subsequently inhibited Treg cells infiltration via regulating PI3K/AKT/mTOR pathway.

CONCLUSIONS:

In CCl₄-induced liver fibrosis mice, Bacteroides acidifaciens and its derived SCFAs exhibit excellent anti-fibrosis effects, which provides a new strategy for liver fibrosis treatment.

01 Aug 2024·JOURNAL OF PHARMACY AND PHARMACOLOGY

GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition

Article

Author: Zhao, Qianying ; Chen, Hongyu ; Wang, Hongzheng ; Yang, Fan ; Guo, Qinglong ; Zhang, Shuai ; Li, Hui ; Zhu, Mengyuan ; Hui, Hui ; Ge, Zheng

Abstract:

Objectives:

GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism.

Methods:

The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC). Xenograft model was constructed to substantiated the synergy effect and its mechanism in vivo.

Results:

GL-V9 was verified to enhance the DNA damage effect of oxaliplatin, so as to synergistically suppress colon cancer cells in vitro and in vivo. In HCT-116 cells, GL-V9 accelerated the degradation of Wee1 and induced the abrogation of cell cycle arrest and mis-entry into mitosis, bypassing the DNA damage response caused by oxaliplatin. Our findings suggested that GL-V9 binding to HSP90 was responsible for the degradation of Wee1 and the vulnerability of colon cancer cells to oxaliplatin. Functionally, overexpression of either HSP90 or WEE1 annulled the synergistic effect of GL-V9 and oxaliplatin.

Conclusions:

Collectively, our findings revealed that GL-V9 synergized with oxaliplatin to suppress CRC and displayed a promising strategy to improve the efficacy of oxaliplatin.

01 Jul 2024·Heliyon

GL-V9 induce apoptosis of CML cells via MAPK signaling pathway

Article

Author: Zhang, Qin ; Xue, Yangyang ; Yu, Xiaoxuan ; Li, Yongming ; Jiang, Fengyu ; Ma, Tonghui

GL-V9, a derivative of wogonin, has shown potent antitumor effects in various cancers, yet its impact on chronic myeloid leukemia (CML) remains unexplored. In this study, we found that GL-V9 significantly decreased the viability of CML cells. Annexin V/PI staining demonstrated that GL-V9 induced apoptosis in a concentration-dependent manner. The JC-1 assay indicated a significant reduction in mitochondrial membrane potential (ΔΨm) in cells treated with GL-V9. Additionally, GL-V9 altered reactive oxygen species (ROS) levels in CML cells. Through transcriptomic sequencing and Western blot analysis, we further revealed that GL-V9 activated the MAPK pathway. These results suggest that GL-V9 is a promising therapeutic candidate for CML.

100 Deals associated with GL-V9

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	China	Southeast University	14 May 2025
Fibrosis, Liver	Preclinical	China	China Pharmaceutical University	01 Dec 2022
Lymphoid neoplasm	Preclinical	China	China Pharmaceutical University	02 Dec 2016