CCG-175472

CCG-175472 is a small-molecule inhibitor that disrupts the TonB-dependent iron uptake pathway in bacteria. Experimental evidence—like TonB overexpression nullifying its effect and blocking TonB-dependent bacteriophage adsorption—supports its role as a TonB function inhibitor.

Functional Role: Inhibitor of TonB System

The TonB system in bacteria is crucial for iron acquisition—it powers the uptake of iron via specific outer-membrane transporters.

• A high-throughput screening study identified CCG-175472 (along with compound 120304) as inhibitors of the TonB-dependent iron acquisition pathway ResearchGatePMC.

• These compounds inhibited bacterial growth under iron-limited conditions. Notably, overexpression of TonB in E. coli reversed the inhibitory effect, strongly suggesting CCG-175472 specifically targets TonB function ResearchGatePMC.

• Additional validation used bacteriophage adsorption assays: normally, bacteriophage λ h 80 binds irreversibly to E. coli via TonB-dependent receptors. One compound (120304) was shown to block this adsorption, and a similar result was observed in a single experiment with CCG-175472—again indicating TonB interference—though follow-up studies were limited due to vendor availability ResearchGatePMC.

0C Short Term -20C Long Term

1) Alejandra Yep et al., Inhibitors of TonB Function Identified by a High-Throughput Screen for Inhibitors of Iron Acquisition in Uropathogenic Escherichia coli CFT073; ASM Journals mBio Vol. 5, No. 2