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HighPlay3 combines cyclic peptide binding design with permeability screening

Academic source · European Journal of Medicinal Chemistry

Source published: 2026-10-16

Site published: 2026-11-03 · Updated: 2026-11-03

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Findings and limitations Industry implications Related developments

What changed

Researchers developed HighPlay3 to balance cyclic peptide target binding and membrane permeability through iterative structural assessment and prediction. Experimental screening produced micromolar binders against MDM2 and GABARAP. Among tested active GABARAP candidates, GAB-D4 showed the highest Caco-2 apparent permeability with no apparent net efflux. These are early laboratory results, not demonstrated human oral bioavailability.

Why it may matter

Integrating permeability early could reduce later optimization cycles, but oral exposure, selectivity, and safety still require substantial experimental validation.

The interpretation above is analysis, not a conclusion attributed to the original source.

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Oral cyclic peptides

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