Delving into the Latest Updates on helvamide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

SOAT1 x SOAT2

Action

inhibitors

Mechanism

SOAT1 inhibitors(Acyl coenzyme A:cholesterol acyltransferase 1 inhibitors), SOAT2 inhibitors(sterol O-acyltransferase 2 inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Kitasato University

Active Organization-

Inactive Organization

Kitasato University

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

We report the discovery and biosynthesis of new piperazine alkaloids‐arizonamides, and their derived compounds‐arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non‐heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3‐alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.

01 Jan 2019·The Journal of antibioticsQ4 · MEDICINE

Helvamide, a new inhibitor of sterol O-acyltransferase produced by the fungus Aspergillus nidulans BF-0142

Q4 · MEDICINE

Article

Author: Fukuda, Takashi ; Furukawa, Takun ; Uchida, Ryuji ; Kobayashi, Keisuke ; Nagai, Kenichiro ; Tomoda, Hiroshi

A new piperazine derivative designated helvamide was isolated as a pair of rotamers (1 and 2) from the culture broth of the fungus Aspergillus nidulans BF-0142 along with a known helvafuranone (3). The structures of 1 and 2 were elucidated based on spectroscopic analyses by the interpretation of one-dimensional and two-dimensional nuclear magnetic resonance data, ROESY (rotational Overhauser effect spectroscopy) correlations, and a chemical method. Helvamide existed as a rotameric mixture (1 and 2) in dimethyl sulfoxide. Helvamide inhibited sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT2) in enzyme-based and cell-based assays using SOAT1-expressing and SOAT2-expressing Chinese hamster ovary (CHO) cells.

100 Deals associated with helvamide

Login to view more data