PEPDG278D

PEPDG278D is a **recombinant, enzymatically inactive mutant of human peptidase D** (also known as prolidase), created by engineering a glycine-to-aspartic acid substitution at position 278. Unlike existing HER2-targeted drugs, PEPDG278D binds to the extracellular domain of **HER2** and **epidermal growth factor receptor (EGFR)**, resulting in potent inhibition of these cancer-driving receptors. By binding HER2, it disrupts protective interactions with mucin 4 and other receptor tyrosine kinases, directs HER2 for degradation, and decreases EGFR signaling, overcoming resistance to current HER2 inhibitors such as trastuzumab. It exhibits strong preclinical efficacy against trastuzumab-resistant HER2-positive breast cancer, showing superior ability to eliminate HER2 and EGFR from cancer cells, with minimal observed toxicity to normal cells. The protein can cross the blood-brain barrier and reduces metastatic brain tumor growth in animal models.

Other names

peptidase D G278Dprolidase G278D mutant