Delving into the Latest Updates on CG-223 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

BET

Mechanism

BET inhibitors(Bromodomain and extra terminal domain protein inhibitors)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseHemic and Lymphatic Diseases+ [1]

Active Indication

Solid tumorLeukemiaOvarian Cancer

Inactive Indication-

Originator Organization

Convergene LLC

Active Organization

Convergene LLC

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Ashihara, Eishi ; Sakashita, Aki ; Strovel, Jeffrey W ; Wada, Makoto ; Fletcher, Steven ; Kasahara, Akiko ; Yoshioka, Makoto ; Nishioka, Keisuke ; Inoue, Takuya ; Kohno, Masataka ; Raje, Mithun ; Hirano, Aiko ; Kida, Takashi ; Kawahito, Yutaka ; Fujioka, Kazuki ; Sagawa, Tomoya ; Nagahara, Hidetake ; Kaneshita, Shunya

Pulmonary fibrosis is a progressive disease with poor prognosis and limited therapeutic options. In this study, we evaluated the potential therapeutic effects of CG223, a novel inhibitor of bromodomain and extra-terminal motif (BET) proteins, on pulmonary fibrosis by focusing on the transforming growth factor-β1 (TGF-β1) pathway. In a murine model of bleomycin-induced pulmonary fibrosis, CG223 attenuated fibrosis while reducing the infiltration of inflammatory cells into the lungs. Fibroblasts expressing BRD4, a member of the BET protein family, were enriched in the tissue regions corresponding to bleomycin-induced fibrotic lesions. Additionally, pulmonary fibroblasts isolated from bleomycin-instilled mice showed a significantly increased association of BRD4 with the promoters of two pro-fibrotic genes linked to the entry into the TGF-β1 autocrine/paracrine loop, thrombospondin 1 (Thbs1) and integrin β3 (Itgb3), as well as with the promoter of a myofibroblast marker gene, actin alpha 2 (Acta2). Subsequent in vitro studies with murine primary lung fibroblasts showed that the mRNA induction of Thbs1, Itgb3, and Acta2 by TGF-β1 can be inhibited by CG223 in a dose-dependent manner. Taken together, CG223-induced BRD4 inhibition suppressed lung fibrogenesis by affecting multiple genes, including those involved in the triggering of the TGF-β1 autocrine/paracrine loop.

100 Deals associated with CG-223

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