Delving into the Latest Updates on CHNQD-01255 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

ARFGEF

Action

inhibitors

Mechanism

ARFGEF inhibitors(ARFGEF family inhibitors)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Hepatocellular Carcinoma

Inactive Indication-

Originator Organization

Ocean University of China

Active Organization

Syngenta Corp.

Ocean University of China

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC23H29NO6

InChIKeyNIVPCXURXHMJGN-CIEKVUGRSA-N

CAS Registry2756173-91-6

Brefeldin A (BFA), a well-known natural Arf-GEFs inhibitor, is effective against hepatocellular carcinoma (HCC), while the poor solubility, serious toxicity, and short half-life limit its potential. Herein, distinct corresponding prodrugs of BFA, including esters 1-15, carbonates 16-24 and 30-32, and carbamates 25-29, were synthesized and evaluated. CHNQD-01255 (16) with improved aqueous solubility (15-20 mg/mL) demonstrated favorable pharmacokinetic profiles. It behaved as expected by undergoing rapid conversion to BFA in vivo, and achieved sufficient high plasma exposure, prolonged half-life, as well as the improved bioavailability of BFA (F = 18.96%). Meanwhile, CHNQD-01255 significantly suppressed tumor growth (TGI = 61.0%) at a dose of 45 mg/kg (p.o.) in the xenograft model. Notably, the improved safety profile of CHNQD-01255 (MTD > 750 mg/kg, p.o.) was confirmed to be superior to that of BFA (MTD < 506 mg/kg). Overall, CHNQD-01255 may serve as a safe and effective new anti-HCC prodrug.

100 Deals associated with CHNQD-01255

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Preclinical	United Kingdom	Syngenta Corp.	12 Sep 2022
Hepatocellular Carcinoma	Preclinical	China	Ocean University of China	12 Sep 2022