Delving into the Latest Updates on IHCH-3064 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

A2aR x HDACs

Action

antagonists, inhibitors

Mechanism

A2aR antagonists(Adenosine A2a receptor antagonists), HDAC inhibitors(Histone deacetylase inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Shanghaitech University

Active Organization-

Inactive Organization

Shanghaitech University

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC25H21N9O2

InChIKeyDZRIVOQHNGLBGP-UHFFFAOYSA-N

CAS Registry2420562-65-6

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A_2A adenosine receptor (A_2AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A_2AR antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A_2AR antagonists, dual-acting compounds incorporating A_2AR antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A_2AR. Compound 24e (IHCH-3064) exhibited potent binding to A_2AR (K_i = 2.2 nM) and selective inhibition of HDAC1 (IC₅₀ = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A_2AR and HDAC are potentially immunotherapeutic agents that are worth further exploring.

100 Deals associated with IHCH-3064

Login to view more data