Delving into the Latest Updates on HJ445A with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

MYOF

Mechanism

MYOF inhibitors(myoferlin inhibitors)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Stomach Cancer

Inactive Indication-

Originator Organization

East China Normal University

Active Organization

East China Normal University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H27N7O2

InChIKeyURMOEUMTLANRDL-UHFFFAOYSA-N

CAS Registry-

Myoferlin (MYOF) mediates the growth and metastasis of various cancers as an emerging therapeutic target by regulating exocytosis and endocytosis. However, the previously reported MYOF inhibitor, 6y, failed to be a favorable candidate agent due to its poor physicochemical properties, such as water solubility, in preclinical studies. Naturally, a novel range of MYOF inhibitors was synthesized and optimized based on the lead compound 6y. The optimal compound HJ445A potently repressed the proliferation of gastric cancer cells with IC₅₀ values of 0.16 and 0.14 μM in MGC803 and MKN45, respectively. Moreover, HJ445A bound to the MYOF-C2D domain with a K_D of 0.17 μM, and HJ445A prevented the migration of gastric cancer cells by reversing the epithelial-mesenchymal transition (EMT) process and inhibited the colony formation of the MKN45 cells in a concentration-dependent manner. Notably, the water solubility of HJ445A was significantly improved compared to 6y, with about 170-fold enhancement. Additionally, HJ445A also demonstrated superior antitumor efficacy in vivo.

100 Deals associated with HJ445A

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