ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats.

@article{Neerup2011ZP2307AN,
  title={ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats.},
  author={Trine S R Neerup and Martin Stahlhut and J{\o}rgen S{\o}berg Petersen and Jens R. Daugaard and Jens-Erik B Jensen and Zhiqi Peng and Jukka Morko and Christian Thorkildsen},
  journal={Bone},
  year={2011},
  volume={48 6},
  pages={
          1319-27
        }
}
Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally… 
Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis
TLDR
The role of PTH signaling pathway in bone remodeling is summarized and investigational analogs targeting this pathway, which may be potential treatments for osteoporosis are summarized.
Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model.
TLDR
It is confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti- FSH polyclonal sera raised by immunizing animals with a recombinant GST-F SHβ fusion protein antigen.
Short Anabolic Peptides for Bone Growth
TLDR
Short peptides offer an important alternative for the development of novel bone‐anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects, and their development for promoting bone growth is summarized.
Parathyroid Hormone (PTH) and PTH-Related Peptide Domains Contributing to Activation of Different PTH Receptor–Mediated Signaling Pathways
TLDR
Several PTH and PTHrP peptides evaluated in this study promote different patterns of biased agonist signaling and may serve as useful tools to further elucidate therapeutically relevant PTH1R signaling in osteoblasts.
Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.
TLDR
This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model and provided valuable information for selecting bone site and observation time in osteoporosis-related study.
Investigational anabolic agents for the treatment of osteoporosis: an update on recent developments
TLDR
This review discusses target molecules and recent advances in the field of anabolic therapy for osteoporosis, and the development of alternative ways of administering PTH receptor ligands is a promising field, especially via the transdermal route.
Food-derived osteogenic peptides towards osteoporosis
Abstract Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased risk of fragility fracture. Osteoporosis occurs when
Pomegranate Fruit as a Rich Source of Biologically Active Compounds
TLDR
The results indicated that PME significantly increased ALP (Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation, and support the fact that pomegranate fruit is indeed a source of biologically active compounds.
Effects of Drugs on Bone Quality
TLDR
It is suggested that while increases in quantity of mineralized tissue present account for much of the reported reduction in fracture risk, drugs that correct the composition and microarchitecture of the bone, returning it to its preosteoporotic status, may provide additional benefits.
Experimental Control for the Ovariectomized Rat Model: Use of Sham Versus Nonmanipulated Animal
TLDR
The data indicate that while OVX animals generally had lower BMD and BMC than animals in either of the control groups, no differences were observed between sham and unmanipulated animals at any of the time points assessed, and studies with longer duration and multiple endpoints are warranted to confirm these results.
...
1
2
...

References

SHOWING 1-10 OF 33 REFERENCES
A comparison of the anabolic effects of rat and bovine parathyroid hormone (1-34) in ovariectomized rats.
TLDR
A relative potency analysis showed that bPTH was approximately 4- to 6-fold relatively more potent than rPTH in increasing distal femoral BMD as well as cancellous bone volume, mineralizing surface, and bone formation rate of proximal tibial metaphyses at comparable dose levels and a given time.
Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure.
TLDR
The pharmacokinetic profiles suggest that the anabolic or catabolic response of bone to PTH(1-34) is determined primarily by the length of time each day that serum concentrations of P TH remain above baseline levels of endogenous PTH and only secondarily by the Cmax or AUC achieved.
Comparison of the Abilities of Human Parathyroid Hormone (hPTH)-(1-34) and [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 to Stimulate Femoral Trabecular Bone Growth in Ovariectomized Rats
Abstract. hPTH-(1-31)NH2, so far the smallest of the potently anabolic N-terminal fragments of the human parathyroid hormone, stimulates trabecular growth in the distal femurs of ovariectomized (OVX)
Bone anabolic effects of PTH(1-34) and salmon calcitonin in ovariectomy- and ovariectomy-steroid-induced osteopenic rats: a histomorphometric and biomechanical study.
TLDR
The results suggest that PTH(1-34) pulsing is able to recover OVX-induced osteopenia in the structure and mechanical strength not only of the cancellous bone but also of the cortical bone, and the anabolic effect can be clinically expected even under steroid medication.
Raloxifene and teriparatide (hPTH 1-34) have complementary effects on the osteopenic skeleton of ovariectomized rats
TLDR
The data suggest that Ral and TPTD have complementary interactions in osteopenic, Ovx rats, and Raloxifene inhibited bone resorption, and reduced high bone turnover without significantly retarding TPTd stimulation of bone formation activity.
Cyclization by a Specific Lactam Increases the Ability of Human Parathyroid Hormone (hPTH)‐(1–31)NH2 to Stimulate Bone Growth in Ovariectomized Rats
  • J. Whitfield, P. Morley, +4 authors J. Barbier
  • Chemistry, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 1997
TLDR
There is now a more potently anabolic derivative of hPTH(1–31)NH2, [Leu27]‐cyclo(Glu22‐Lys26)‐hPTH (1-31) NH2, which might ultimately prove to be one of the more effective therapeutics for osteoporosis.
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
TLDR
Treatment of postmenopausal osteoporosis with parathyroid hormone decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated.
In Vitro & In Vivo Effect of Parathyroid Hormone Analogue (1-14) Containing α-amino-iso-butyric Acid Residue (Aib)1,3
TLDR
The findings suggest that unacetylated Aib1,3PTH (1-14) did not exhibit any anabolic effects at the bones of ovariectomized rats.
Prolonged Treatments With Antiresorptive Agents and PTH Have Different Effects on Bone Strength and the Degree of Mineralization in Old Estrogen-Deficient Osteoporotic Rats
TLDR
Treatment of estrogen‐deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.
Mechanisms Involved in Skeletal Anabolic Therapies
TLDR
The finding that concurrent treatment with bisphosphonates impairs the anabolic response to PTH, adds to other clues that osteoclast activity is necessary to complement the direct effect that PTH has in promoting differentiation of committed osteoblast precursors.
...
1
2
3
4
...