Delving into the Latest Updates on PARP7/HDACs dual inhibitors(Hangzhou Normal University) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

HDAC inhibitors(Histone deacetylase inhibitors), PARP-7 inhibitors(TCDD-inducible poly [ADP-ribose] polymerase inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Hangzhou Normal University

Active Organization

Hangzhou Normal University

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC29H33F3N8O6

InChIKeyBIFMDHUVYGGFCU-GHOSXJJBSA-N

CAS Registry3030144-11-4

Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated in vitro and in vivo experiments. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.

100 Deals associated with PARP7/HDACs dual inhibitors(Hangzhou Normal University)

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