BRD4 inhibitors(Bromodomain-containing protein 4 inhibitors), HDAC inhibitors(Histone deacetylase inhibitors), JAK inhibitors(Janus kinase inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Shandong University

Active Organization

Shandong University

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC24H28N6O3

InChIKeyJUIHREVFVXLZPR-UHFFFAOYSA-N

CAS Registry2755325-84-7

100 Clinical Results associated with 25-ap

100 Translational Medicine associated with 25-ap

100 Patents (Medical) associated with 25-ap

Literatures (Medical) associated with 25-ap

26 Oct 2023·Journal of medicinal chemistryQ1 · MEDICINE

Discovery of Novel Fedratinib-Based HDAC/JAK/BRD4 Triple Inhibitors with Remarkable Antitumor Activity against Triple Negative Breast Cancer.

Q1 · MEDICINE

Article

Author: Zhang, Jin'ge ; Liu, Fengling ; Meng, Hongwei ; Chai, Qipeng ; Geng, Yinping ; Li, Shunda ; Zhang, Yingjie ; Liu, Mengyang ; Zhang, Yu ; Zheng, Yichao ; Li, Jintao ; Zhao, Chunlong ; Li, Mengzhe

Multitarget HDAC inhibitors capable of simultaneously blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway hold great potential for the treatment of TNBC and other solid tumors. Herein, novel Fedratinib-based multitarget HDAC inhibitors were rationally designed, synthesized, and biologically evaluated, among which compound 25ap stood out as a potent HDAC/JAK/BRD4 triple inhibitor. Satisfyingly, compound 25ap led to concurrent inhibition of HDACs and the BRD4-LIFR-JAK1-STAT3 signaling pathway, which was validated by hyper-acetylation of histone and α-tubulin, hypo-phosphorylation of STAT3, downregulation of LIFR, MCL-1, and c-Myc in MDA-MB-231 cells. The multitarget effects of 25ap contributed to its robust antitumor response, including potent antiproliferative activity, remarkable apoptosis-inducing activity, and inhibition of colony formation. Notably, 25ap possessed an acceptable therapeutic window between normal and cancerous cells, desirable in vitro metabolic stability in mouse microsome, and sufficient in vivo exposure via intraperitoneal administration. Additionally, the in vivo antitumor potency of 25ap was demonstrated in an MDA-MB-231 xenograft model.

Journal of Medicinal Chemistry

Discovery of Novel Fedratinib-Based HDAC/JAK/BRD4 Triple Inhibitors with Remarkable Antitumor Activity against Triple Negative Breast Cancer

Author: Zhang, Jin'ge ; Liu, Fengling ; Meng, Hongwei ; Liu, Mengyang ; Chai, Qipeng ; Li, Shunda ; Zhang, Yingjie ; Zheng, Yichao ; Li, Jintao ; Zhao, Chunlong ; Li, Mengzhe ; Zhang, Yu ; Geng, Yinping

Multitarget HDAC inhibitors capable of simultaneously blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway hold great potential for the treatment of TNBC and other solid tumors.Herein, novel Fedratinib-based multitarget HDAC inhibitors were rationally designed, synthesized, and biol. evaluated, among which compound 25ap stood out as a potent HDAC/JAK/BRD4 triple inhibitor.Satisfyingly, compound 25ap led to concurrent inhibition of HDACs and the BRD4-LIFR-JAK1-STAT3 signaling pathway, which was validated by hyper-acetylation of histone and α-tubulin, hypo-phosphorylation of STAT3, downregulation of LIFR, MCL-1, and c-Myc in MDA-MB-231 cells.The multitarget effects of 25ap contributed to its robust antitumor response, including potent antiproliferative activity, remarkable apoptosis-inducing activity, and inhibition of colony formation.Notably, 25ap possessed an acceptable therapeutic window between normal and cancerous cells, desirable in vitro metabolic stability in mouse microsome, and sufficient in vivo exposure via i.p. administration.Addnl., the in vivo antitumor potency of 25ap was demonstrated in an MDA-MB-231 xenograft model.

100 Deals associated with 25-ap

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Discovery	China	Shandong University	05 Oct 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

25-ap

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation