FimH-mediated cellular adhesion to mannosylated proteins is critical in the ability of uropathogenic E. coli (UPEC) to colonize and invade the bladder epithelium during urinary tract infection. We describe the discovery and optimization of potent small-molecule FimH bacterial adhesion antagonists based on alpha-d-mannose 1-position anomeric glycosides using X-ray structure-guided drug design. Optimized biarylmannosides display low nanomolar binding affinity for FimH in a fluorescence polarization assay and submicromolar cellular activity in a hemagglutination (HA) functional cell assay of bacterial adhesion. X-ray crystallography demonstrates that the biphenyl moiety makes several key interactions with the outer surface of FimH including pi-pi interactions with Tyr-48 and an H-bonding electrostatic interaction with the Arg-98/Glu-50 salt bridge. Dimeric analogues linked through the biaryl ring show an impressive 8-fold increase in potency relative to monomeric matched pairs and represent the most potent FimH antagonists identified to date. The FimH antagonists described herein hold great potential for development as novel therapeutics for the effective treatment of urinary tract infections.
Pharmacology, Toxicology and Pharmaceutical Science
5
3%
Other
24
14%
Unknown
39
23%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 February 2026.
All research outputs
#2,976,449
of 33,849,731 outputs
Outputs from Journal of Medicinal Chemistry
#2,540
of 27,721 outputs
Outputs of similar age
#11,099
of 149,071 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#15
of 129 outputs
Altmetric has tracked 33,849,731 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 27,721 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 149,071 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 129 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.
