Work

Discovery of Orally Active and Nonsteroidal Farnesoid X Receptor (FXR) Antagonist with Propensity for Accumulation and Responsiveness in Ileum

Year: 2021

Type: article

Abstract: We describe the discovery of analog 15 (FLG249), which is an orally active and nonsteroidal farnesoid X receptor (FXR) antagonist in mice with unique profiles, such as a propensity for ileum distribution and the significant control in the expression level of three FXR target genes in mouse ileum. Key design features incorporated in 15 were the introduction of metabolically stable groups in potent and metabolically labile antagonist 9 . Our pursuit ultimately identified FXR antagonist 15, which has enabled its assessment in a drug discovery program.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.0c00640

Authors: Naoki Teno, Yusuke Iguchi, Keisuke Oda, Yukiko Yamashita, Arisa Masuda, Ko Fujimori, Mizuho Une, Keigo Gohda

Institutions: Hiroshima International University, Osaka University of Pharmaceutical Sciences

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W3132913744

FWCI: 1.801

Cites: 38

Cited by: 22

Related to: 10