Author: Wang, Ning ; Shen, Liang ; Zhou, Ying ; Ji, Shi-Kun ; Liu, Ying ; Liu, Hui-Min ; Wang, Shao-Peng ; Xiong, Xiao-Peng ; Zheng, Yi-Chao ; Liu, Hong-Min ; Chen, He-Xiang ; Dai, Xing-Jie ; Wu, Jiang-Wan

Recently, histone lysine specific demethylase 1 (LSD1) has become an emerging and promising target for cancer immunotherapy. Herein, based on our previously reported LSD1 inhibitor DXJ-1 (also called 6x), a series of novel acridine-based LSD1 inhibitors were identified via structure optimizations. Among them, compound 5ac demonstrated significantly enhanced inhibitory activity against LSD1 with an IC₅₀ value of 13 nM, about 4.6-fold more potent than DXJ-1 (IC₅₀ = 73 nM). Molecular docking studies revealed that compound 5ac could dock well into the active site of LSD1. Further mechanism studies showed that compound 5ac inhibited the stemness and migration of gastric cancer cells, and reduced the expression of PD-L1 in BGC-823 and MFC cells. More importantly, BGC-823 cells were more sensitive to T cell killing when treated with compound 5ac. Besides, the tumor growth was also suppressed by compound 5ac in mice. Together, 5ac could serve as a promising candidate to enhance immune response in gastric cancer.

01 Sep 2023·Bulletin of Experimental Biology and Medicine

α2C-Adrenergic Receptor Blockade Inhibits Langendorff-Isolated Rat Heart Work

Article

Author: Zefirov, A L ; Khabibrakhmanov, I I ; Khisamieva, L I ; Ziyatdinova, N I ; Zefirov, T L

We studied the effect of selective α_2C-adrenergic receptor antagonist JP-1302 in concentrations of 10^-9-10^-6 M on inotropy, chronotropy, and coronary flow in the Langendorff-isolated rat heart. JP-1302 in all studied concentrations decreased the left-ventricular myocardium force contraction, HR, and coronary flow. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10^-7 M. The least pronounced decrease in the studied parameters was observed at JP-1302 concentrations of 10^-8 and 10^-9 M. The obtained data indicate the participation of this subtype of α₂-adrenergic receptors in the regulation of activity of isolated adult rats heart.

01 Jun 2023·Nature Biotechnology

A proteome-wide atlas of drug mechanism of action

Article

Author: Gygi, Steven P ; Van Vranken, Jonathan G ; Li, Jiaming ; Schweppe, Devin K ; Mitchell, Dylan C ; Huttlin, Edward L ; Kuljanin, Miljan ; Bulloch, Nathan

Defining the cellular response to pharmacological agents is critical for understanding the mechanism of action of small molecule perturbagens. Here, we developed a 96-well-plate-based high-throughput screening infrastructure for quantitative proteomics and profiled 875 compounds in a human cancer cell line with near-comprehensive proteome coverage. Examining the 24-h proteome changes revealed ligand-induced changes in protein expression and uncovered rules by which compounds regulate their protein targets while identifying putative dihydrofolate reductase and tankyrase inhibitors. We used protein-protein and compound-compound correlation networks to uncover mechanisms of action for several compounds, including the adrenergic receptor antagonist JP1302, which we show disrupts the FACT complex and degrades histone H1. By profiling many compounds with overlapping targets covering a broad chemical space, we linked compound structure to mechanisms of action and highlighted off-target polypharmacology for molecules within the library.

100 Deals associated with JP-1302

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Psychotic Disorders	Phase 1	FI	Orion Oyj	15 Jan 2007
Depressive Disorder, Major	Phase 1	GB	Juvantia Pharma Oy	-
Brain Cancer	Preclinical	SE	Karolinska Institutet	09 Apr 2024
Stomach Cancer	Preclinical	CN	Zhengzhou University	29 Jul 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

Chat with Hiro

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

JP-1302

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation