Delving into the Latest Updates on HWL-088 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

GPR40

Mechanism

GPR40 agonists(Free fatty acid receptor 1 agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus

Inactive Indication-

Originator Organization

Guangdong Pharmaceutical University

Active Organization

Guangdong Pharmaceutical University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H19FO4

InChIKeyNJYJBYPNDWNZAH-UHFFFAOYSA-N

CAS Registry2378617-96-8

Nonalcoholic fatty liver (NAFLD), a chronic progressive liver disease, is highly correlated with pathoglycemia, dyslipidemia and oxidative stress. The free fatty acid receptor 1 (FFA1) agonists have been reported to improve liver steatosis and fibrosis, and the peroxisome proliferator-activated receptor δ (PPARδ) plays a synergistic role with FFA1 in energy metabolism and fibrosis. HWL-088, a PPARδ/FFA1 dual agonist, exerts better glucose-lowering effects than the representative FFA1 agonist TAK-875. However, the ability of HWL-088 to protect NAFLD was unknown. This study aimed to discover a new strategy for the treatment of NAFLD.

Methods:

The methionine- and choline-deficient diet (MCD)-induced Nonalcoholic steatohepatitis (NASH) model was constructed to evaluate the effects of HWL-088.

Key findings:

Administration of HWL-088 exerted multiple benefits on glucose control, lipid metabolism and fatty liver. Further mechanism research indicated that HWL-088 promotes lipid metabolism by decreasing lipogenesis and increasing lipolysis. Moreover, HWL-088 attenuates NASH by regulating the expression levels of genes related to inflammation, fibrosis and oxidative stress.

Conclusions:

These positive results indicated that PPARδ/FFA1 dual agonist HWL-088 might be a potential candidate to improve multiple pathogenesis of NASH.

100 Deals associated with HWL-088

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