title: ZT-031, a cyclized analog of parathyroid hormone(1-31) for the potential treatment of osteoporosis.
abstract: ZT-031 is a cyclic 31-amino acid analog of parathyroid hormone (PTH) that is in development by Zelos Therapeutics Inc for the treatment of osteoporosis and other bone-related disorders. ZT-031 activates the PTH type 1 receptor - the molecular target of the currently marketed osteogenic peptides PTH and PTH(1-34). Daily subcutaneous injections of ZT-031 prevented bone loss and replaced bone that had already been lost in an ovariectomized rat model of osteoporosis. Daily subcutaneous injections of ZT-031 in gonad-intact monkeys increased bone mineral density (BMD) at cortical and cancellous bone sites and increased serum levels of bone formation markers. The daily subcutaneous administration of ZT-031 to postmenopausal women with osteoporosis elicited a dose-dependent increase in BMD of the lumbar spine, proximal femur and total hip area. Plasma levels of bone formation markers were significantly increased above baseline after 1 month of dosing, and prior to increases in bone resorption markers. ZT-031 was demonstrated to be safe and well tolerated; episodes of hypercalcemia were infrequent and observed with a frequency greater than with placebo only at the highest doses tested for the drug. Although available data are limited, the results obtained following treatment with ZT-031 have generally been at least as favorable as those obtained with other osteogenic PTH peptides. A novel dosing paradigm has been planned for the drug.
authors.affiliation: MetisMedica, 32 Elgin Avenue, Toronto, ON, M5R 1G6, Canada. nemeth.ed@gmail.com
authors.forename: Edward F
authors.initials: EF
authors.lastname: Nemeth
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D010330:Patents as Topic; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D011323:Primates; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D010456:Peptides, Cyclic; C533780:ZT-031