PROLYL HYDROXYLASE INHIBITORS AS RADIATION MITIGATORS AND RADIATION PROTECTORS
Radiology
This discovery provides a novel platform to use Prolyl hydroxylase inhibitors prophylactically or therapeutically to prevent radiation-induced damage of the healthy tissue. The discovery finds application in medical interventions, such as for the treatment of cancer, or in accidental exposure such as radiation leakage at a nuclear power plant.
Prolyl Hydroxylase (PH) inhibitors form a novel class of therapeutics that can function as radiation mitigators by protecting healthy cells from the cytotoxic effects of ionizing radiation exposure. PH inhibitors may be administered before, during or even 48 hours after radiation exposure. These inhibitors may be administered either locally or systemically and in doses that inhibit injury of noncancerous tissues and cells, without interfering with the killing of cancerous tissues and cells. Inhibition of PHs, in particular the Hypoxia Inducible Factor l -prolyl hydroxylase (HIF-PH) sub-family blocks HIF-la degradation, leading to the transcriptional activation of genes that promote adaptation to hypoxia and protect the cells from radiation damage. Inhibition of another PH subfamily, the lysine demethylase sub-family (KDM), increases levels of histone 3 lysine 9 methylation (H3K9me3) across the chromatin, promoting both increased activation of the ATM (Ataxia Telangiectasia Mutated) kinase and changes in chromatin structure which can facilitate repair of double-strand DNA breaks caused by radiation.
Inventor: PRICE, Brendan, D. | SUN, Yingli
Priority Number: WO2012037212A1
IPC Current: A61K003846 | C12N000948 | C12N000999
Assignee Applicant: Dana-Farber Cancer Institute Inc.
Title: PROLYL HYDROXYLASE INHIBITORS AS RADIATION MITIGATORS AND RADIATION PROTECTORS | INHIBITEURS DE PROLYL HYDROXYLASE À TITRE D'AGENTS D'ATTÉNUATION DU RAYONNEMENT ET DE PROTECTION CONTRE LE RAYONNEMENT
Usefulness: PROLYL HYDROXYLASE INHIBITORS AS RADIATION MITIGATORS AND RADIATION PROTECTORS | INHIBITEURS DE PROLYL HYDROXYLASE À TITRE D'AGENTS D'ATTÉNUATION DU RAYONNEMENT ET DE PROTECTION CONTRE LE RAYONNEMENT
Summary: For inhibiting tissue injury in a subject resulting from exposure to radiation; and reducing the number of double-stranded DNA breaks in the cells (claimed).
生物医学
DNA /基因工程
美国
