Discovery of HDAC6, HDAC8, and 6/8 Inhibitors and Development of Cell-Based Drug Screening Models for the Treatment of TGF-β-Induced Idiopathic Pulmonary Fibrosis.

Q1 · MEDICINE

Article

Author: Yu, Wei-Chieh ; Lin, Chen-Si ; Chern, Ji-Wang ; Shao, Chi-Hsuan ; Ho, Yi-Hsun ; Lin, Shau-Ping ; Jagtap, Ajit Dhananjay ; Yeh, Tsung-Yu ; So, Dorothy Kazuno ; Chong, Patrick Chun Theng ; Peng, Guan-Ru ; Ye, Chih-Hung ; Yu, Shu-Han ; Lin, Shuei-Liong ; Yu, Chao-Wu ; Yap, Kah Yi

Idiopathic pulmonary fibrosis is incurable, and its progression is difficult to control and thus can lead to pulmonary deterioration. Pan-histone deacetylase inhibitors such as SAHA have shown potential for modulating pulmonary fibrosis yet with off-target effects. Therefore, selective HDAC inhibitors would be beneficial for reducing side effects. Toward this goal, we designed and synthesized 24 novel HDAC6, HDAC8, or dual HDAC6/8 inhibitors and established a two-stage screening platform to rapidly screen for HDAC inhibitors that effectively mitigate TGF-β-induced pulmonary fibrosis. The first stage consisted of a mouse NIH-3T3 fibroblast prescreen and yielded five hits. In the second stage, human pulmonary fibroblasts (HPFs) were used, and four out of the five hits were tested for caco-2 permeability and liver microsome stability to give two potential leads: J27644 (15) and 20. This novel two-stage screen platform will accelerate the discovery and reduce the cost of developing HDAC inhibitors to mitigate TGF-β-induced pulmonary fibrosis.

Journal of Medicinal Chemistry

Discovery of HDAC6, HDAC8, and 6/8 Inhibitors and Development of Cell-Based Drug Screening Models for the Treatment of TGF-β-Induced Idiopathic Pulmonary Fibrosis

Author: Yu, Wei-Chieh ; Chern, Ji-Wang ; So, Dorothy Kazuno ; Lin, Shau-Ping ; Yu, Chao-Wu ; Jagtap, Ajit Dhananjay ; Yeh, Tsung-Yu ; Lin, Chen-Si ; Chong, Patrick Chun Theng ; Lin, Shuei-Liong ; Peng, Guan-Ru ; Ho, Yi-Hsun ; Ye, Chih-Hung ; Yu, Shu-Han ; Shao, Chi-Hsuan ; Yap, Kah Yi

Idiopathic pulmonary fibrosis is incurable, and its progression is difficult to control and thus can lead to pulmonary deterioration.Pan-histone deacetylase inhibitors such as SAHA have shown potential for modulating pulmonary fibrosis yet with off-target effects.Therefore, selective HDAC inhibitors would be beneficial for reducing side effects.Toward this goal, we designed and synthesized 24 novel HDAC6, HDAC8, or dual HDAC6/8 inhibitors and established a two-stage screening platform to rapidly screen for HDAC inhibitors that effectively mitigate TGF-β-induced pulmonary fibrosis.The first stage consisted of a mouse NIH-3T3 fibroblast prescreen and yielded five hits.In the second stage, human pulmonary fibroblasts (HPFs) were used, and four out of the five hits were tested for caco-2 permeability and liver microsome stability to give two potential leads: J27644 (15) and 20.This novel two-stage screen platform will accelerate the discovery and reduce the cost of developing HDAC inhibitors to mitigate TGF-β-induced pulmonary fibrosis.

100 Deals associated with J-27644

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Idiopathic Pulmonary Fibrosis	Discovery	Taiwan Province	National Taiwan University	18 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

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

J-27644

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation