BRD4780

BRD4780 (also known as AGN 192403) is a small molecule that acts as a ligand and modulator of the cargo receptor transmembrane p24 trafficking protein 9 (TMED9). Originally developed by Allergan as a selective imidazoline I1 receptor antagonist for hypertension, it was later repurposed by researchers at the Broad Institute of MIT and Harvard. BRD4780 binds directly to TMED9, releasing trapped misfolded proteins—such as mutant mucin 1 (MUC1-fs) and mutant uromodulin (UMOD)—from TMED9-containing vesicles in the early secretory pathway and re-routing them to the lysosome for degradation. This clearance of toxic protein aggregates alleviates endoplasmic reticulum (ER) stress and prevents cell death, making BRD4780 a promising therapeutic lead for autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1 and ADTKD-UMOD) and other toxic proteinopathies.

Other names

(1R,2R,3R,4S)-rel-3-(1-methylethyl)-bicycloheptan-2-amine hydrochloride(±)-2-endo-amino-3-exo-isopropylbicycloheptane hydrochlorideAGN 192403 hydrochlorideAGN192403 hydrochlorideAGN-192403 hydrochlorideBRD4780 hydrochlorideBRD-4780 hydrochlorideBRD 4780 hydrochloride