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 tibia. Female C57BL/6 mice were injected with vehicle, 320 µg/kg, or 1000 µg/kg [W2]PTH(1-33)-CBD as a single injection. Animal behavior, body weight, mortality, and biochemical and organ toxicity assays showed no significant chan

SUBMITTER: Ponnapakkam T 

PROVIDER: S-EPMC12281181 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature