Delving into the Latest Updates on BH-400 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BH 400, BH400

Target

PPARα x STING

Mechanism

PPARα modulators(Peroxisome proliferator-activated receptor α modulators), STING1 modulators(Stimulator of interferon genes modulators)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseEye Diseases

Active Indication

Diabetic Retinopathy

Inactive Indication-

Originator Organization

University of Minnesota

Active Organization

University of Minnesota

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Inflammatory retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) are prominent causes of blindness in industrialized countries. The complexity of these diseases, involving diverse cell types and pathways that give rise to a multifactorial pathogenesis, complicates drug discovery. As such, therapies exhibiting polypharmacology are expected to improve outcomes through broader disease stage coverage and beneficial spatiotemporal effects. We report herein the first dual modulator of PPARα and STING, two targets tied to disparate pathologies in retinal diseases. Recognizing structural similarities between a reported STING inhibitor SN-013 and our previously described PPARα agonist A229, we designed BH400, which agonizes PPARα (EC₅₀ = 1.2 μM) and inhibits STING (IC₅₀ = 8.1 μM). BH400 demonstrates superior protection over single-target PPARα or STING modulation in microglial and photoreceptor cells. These findings provide compelling evidence for the potential benefit of polypharmacology in common retinal diseases through dual PPARα/STING modulation, motivating further studies.

ACS Medicinal Chemistry Letters

Design and Assessment of First-Generation Heterobifunctional PPARα/STING Modulators

Article

Author: Hu, Bo ; Duerfeldt, Adam S. ; Cui, Yi ; Ma, Jian-Xing ; Lee, Julia J.

Inflammatory retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) are prominent causes of blindness in industrialized countries. The complexity of these diseases, involving diverse cell types and pathways that give rise to a multifactorial pathogenesis, complicates drug discovery. As such, therapies exhibiting polypharmacology are expected to improve outcomes through broader disease stage coverage and beneficial spatiotemporal effects. We report herein the first dual modulator of PPARα and STING, two targets tied to disparate pathologies in retinal diseases. Recognizing structural similarities between a reported STING inhibitor SN-013 and our previously described PPARα agonist A229, we designed BH400, which agonizes PPARα (EC₅₀ = 1.2 μM) and inhibits STING (IC₅₀ = 8.1 μM). BH400 demonstrates superior protection over single-target PPARα or STING modulation in microglial and photoreceptor cells. These findings provide compelling evidence for the potential benefit of polypharmacology in common retinal diseases through dual PPARα/STING modulation, motivating further studies.

100 Deals associated with BH-400

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