drug conjugates

Key Stability Hurdles for Targeting Peptides in PDCs and ADCs

Peptide instability stands out as the top reason peptide-drug conjugates fail to advance to clinical use, unlike antibody-drug conjugates which more commonly stumble on linker or payload problems. Linear peptides break down quickly in serum due to proteases, lose their binding shape, and get cleared by the kidneys before hitting tumors, causing low payload delivery and unintended toxicity. This article details the chemical and biological stability issues, from proteolysis to linker failures, that undermine these targeted therapies.