Histone lysine demethylase 4D (KDM4D) is a critical player in the regulation of tumorigenesis, emerging as a potential target for developing anti-tumor agents. In this study, a series of KDM4D inhibitors containing the 4,6-diarylquinoxaline scaffold were prepared based on the previously discovered hit compound QD-1. Among these inhibitors, 33a was the most potent compound, with an IC₅₀ value of 0.62 μM. In an in vitro assay, 33a showed a superior ability to inhibit the viability of liver cancer Huh-7 cells with IC₅₀ = 5.23 μM. 33a exhibits significant effects in inhibiting cell cycle progression and proliferation of liver cancer cells, as well as suppressing cell migration. This work provided a promising scaffold for developing KDM4D inhibitors, as well as a lead compound for the development of anti-tumor drugs targeting KDM4D.

01 Apr 2023·Bioorganic & Medicinal Chemistry

An ATG4B inhibitor blocks autophagy and sensitizes Sorafenib inhibition activities in HCC tumor cells

Article

Author: Wan, Wei ; Zhang, Naixia ; Xie, Yanqiu ; Xu, Pan ; Lu, Jing ; Luo, Cheng ; Xiao, Weilie ; Zhang, Ruihan ; Ding, Yiluan ; Ni, Dongxuan ; Zhang, Yuanyuan ; Fan, Shijie ; Zhao, Kehao

Autophagy related 4B (ATG4B) which regulates autophagy by promoting the formation of autophagosome through reversible modification of LC3, is closely related to cancer cell growth and drug resistance, and therefore is an attractive therapeutic target. Recently, ATG4B inhibitors have been reported, yet with drawbacks including weak potency. To discover more promising ATG4B inhibitors, we developed a high-throughput screening (HTS) assay and identified a new ATG4B inhibitor named DC-ATG4in. DC-ATG4in directly binds to ATG4B and inhibits its enzyme activity with an IC₅₀ of 3.08 ± 0.47 μM. We further confirmed that DC-ATG4in is an autophagy inhibitor and blocks autophagy induced by Sorafenib in Hepatocellular Carcinoma (HCC) cells. More importantly, combination of DC-ATG4in with Sorafenib synergized the cancer cell killing effect and proliferation inhibition activities on HCC cells. Our data suggested that inactivation of autophagy via ATG4B inhibition may be a viable strategy to sensitize existing targeted therapy such as Sorafenib in the future.

100 Deals associated with DC-ATG4in

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Preclinical	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	27 Mar 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

DC-ATG4in

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation