Acute toxicological evaluation of bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist to inhibit breast cancer metastases to bone

Abstract The present study evaluates the in vivo acute toxicological profile and drug distribution of a novel bone-targeted parathyroid hormone-related peptide (PTHrP) antagonist for bone metastatic breast cancer. [W2]PTH(1−33)-CBD was created by fusing PTHrP antagonist peptide to the bacterial collagen-binding domain (CBD) of ColG collagenase from Clostridium histolyticum to target the drug to type 1 collagen in bone. Acting as an inverse agonist at the PTH/PTHrP receptor, [W2]PTH(1−33)-CBD induced apoptosis in breast cancer cells and reduced tumor burden in mouse