Delving into the Latest Updates on 4010B-30 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

APOA1

Mechanism

APOA1 inhibitors(Apolipoprotein A-I inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Atherosclerosis

Inactive Indication-

Originator Organization

Institute of Medicinal Biotechnology Academy of Medical Scien

Active Organization

Institute of Medicinal Biotechnology Academy of Medical Scien

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

OBJECTIVEApolipoprotein (Apo) A-I is the major lipoprotein content of HDL and upregulating endogenous ApoA-I expression has been proposed as a desirable approach to raise the functional HDL. In this study we investigated the effect of a novel small molecule 4010B-30 on transcriptional regulation of ApoA-I gene in HepG2 cells, and the influence on the level of ApoA-I expression and function. Then the mechanisms by which 4010B-30 regulated ApoA-I expression was further explored.METHODS AND RESULTSIn human hepatic HepG2 cells, 4010B-30 increased the mRNA level and the protein production of ApoA-I both in cell lysates and media. The 4010B-30-induced ApoA-I containing particles increased cholesterol efflux from RAW264.7 macrophages. 4010B-30 also upregulated ABCA1 expression confirmed by transcriptional activity assay and Western blot analysis in both HepG2 and RAW264.7 cells. Promoter luciferase assay was used to identify the 4010B-30-responsive region which is mapped to the proximal -277bp region of the ApoA-I promoter. Further study indicated that the regulation of 4010B-30 on ApoA-I transcription or protein expression in HepG2 cells was abrogated with the suppression of PPARγ by its small interfering RNA or a specific inhibitor, GW9662.CONCLUSIONSThese findings suggest that the novel small molecular upregulator 4010B-30 increases ApoA-I gene expression, thereby enhances its function of promoting cholesterol efflux, as well as ABCA1 expression in vitro, and activation of PPARγ is required for 4010B-30 to induce hepatic ApoA-I production.

100 Deals associated with 4010B-30

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