Delving into the Latest Updates on FR-129169 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ACAT1

Mechanism

ACAT1 inhibitors(ACAT inhibitors)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Hypercholesterolemia

Originator Organization

Astellas Pharma, Inc.

Active Organization-

Inactive Organization

Astellas Pharma, Inc.

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC30H37NO2

InChIKeyXUCJTVYTRXSOJC-UHFFFAOYSA-N

CAS Registry143895-84-5

FR129169 (FR) (N-(1,2-diphenylethyl)-2-octyloxyphenylacetamide) has been found to inhibit acyl-CoA:cholesterol acyltransferase (ACAT) activities in intestinal microsomes of rats and rabbits and the liver homogenate of rats with IC50 values of around 1.0 x 10(-7) M. The inhibitory activity was 2-3 times more potent than that of CI 976 (CI). When FR in a dose of 10 mg/kg/day was administered as a dietary admixture, plasma cholesterol levels were normalized in rats fed a high cholesterol diet, but lower doses of FR had no effect. Similar results were obtained in the rats treated with CI. The ex vivo study where hepatic ACAT activity was measured after oral dosing of the two inhibitors revealed that ACAT activity was significantly reduced in rats treated with FR in a dose of 10 mg/kg/day, while CI reduced the activity at lower doses such as 0.1 and 1 mg/kg/day. Since FR was not orally absorbed, it is speculated that the inhibitory activity of FR on hepatic ACAT in the ex vivo study results from the reduction of plasma cholesterol levels. These results suggest that FR exerted cholesterol-lowering activity mainly through inhibition of intestinal ACAT activity. The significance of intestinal ACAT inhibition by FR for therapeutic treatment of hypercholesterolemia is discussed.

100 Deals associated with FR-129169

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