Dipeptide TGF-beta Inhibitors for Selective Cancer Therapy

The patent applies local quality by designing TGF-β inhibitors that selectively target disease-related TGF-β activity in specific tissues (liver, kidney, lung, heart) while preserving homeostatic TGF-β signaling in other contexts. This is achieved through tissue-specific delivery mechanisms and selective inhibition strategies that differentiate between pathological and physiological TGF-β functions.

The patent inverts the conventional approach by using TGF-β-activated markers (SAMs) as positive indicators for therapy administration. Instead of broadly inhibiting TGF-β and hoping to avoid adverse effects, the invention activates TGF-β signaling pathways selectively in diseased tissues, then uses the resulting SAMs to guide precise inhibitor delivery only to those activated sites, thereby treating disease while preserving normal TGF-β function.

The patent applies parameter changes by modifying the chemical structure of TGF-β inhibitor peptides through non-natural amino acid substitutions, cyclization, and conjugation to carrier molecules. These structural parameter changes dramatically improve plasma half-life from minutes to hours or days, while maintaining or enhancing TGF-β binding affinity. The modified peptides also become more resistant to proteolytic degradation, reducing synthesis costs by lowering dosing frequency.

The patent creates composite inhibitor molecules by combining TGF-β binding peptides with carrier proteins (e.g., albumin, immunoglobulins) or nanoparticle systems. These composite structures provide both the specific TGF-β inhibition function and the extended circulation half-life properties of the carrier, while also enabling targeted delivery to diseased tissues through active targeting ligands or passive accumulation mechanisms.