Endocrine Abstracts

AZP-3601, a long-acting PTH/PTHrP(1-36) analog, is a candidate new treatment option for hypoparathyroidism (HP). As compared to conventional PTH(1-34), AZP-3601 binds with higher affinity to the R0 conformation of the PTH-1 receptor, resulting in prolonged signaling and sustained elevations in blood calcium (Ca++) in vivo, despite a very short circulating half-life. We assessed whether repeated injection of AZP-3601 into TPTX rats at doses aimed to normalize serum C...

Medical treatment of acromegaly is based on either suppressing pituitary GH secretion or inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of IGF1. AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) derived from peptide sequences discovered using a unique, cell-free in vitro transcription-translation system screened against the human GHR, and that was optimized by rational design to increase...

The key metabolic hormone, leptin, acts in part through the liver to regulate glucose homeostasis, as well as the maturation of both adipocytes and osteoblasts. These actions have been demonstrated to be mediated by insulin-like growth factor binding protein 2 (IGFBP-2), independent of its ability to bind IGF1. The effects of IGFBP-2 on adipocyte and osteoblast maturation can be localized to a short peptide sequence within the unique heparin binding domain (HBD-1) of IGFBP-2. ...

Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bi...

Eneboparatide (AZP-3601) is a novel, synthetic, 36-amino-acid peptide agonist of the parathyroid hormone type 1 receptor (PTHR1), with potent selectivity for the R0 conformation. This results in prolonged calcemic responses, while having a short circulating half-life. Eneboparatide is being developed for the treatment of chronic hypoparathyroidism (cHP). Studies in hypoparathyroid animal models and, most recently, in hypoparathyroid patients, have demonstrated that eneboparati...

Medical treatment of acromegaly is based on either suppressing pituitary growth hormone (GH) secretion or by inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of insulin-like growth factor 1 (IGF1). AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) with KD of 1.9 nM for the human GHR. Previously, AZP-3813 was demonstrated to suppress IGF1 secretion in juvenile rats in a dose-rela...

The increasing use of somatostatin (SRIF) analogues prompted extensive investigations on SRIF receptor (SSR) in human tumours. Human prostate cancer (PCa) may differentially express SSRs from the normal tissue. Moreover, SSR and dopamine (D) receptors (DR) may interact to form homo- and heterodimers with enhanced functional activity. In the present study, using the human androgen-dependent PCa cell line LNCaP, we investigated: 1) SSR and DR subtype expression in different cult...

Somatostatin (SRIF) has been demonstrated to inhibit in vitro proliferation of normal and transformed cells via SRIF receptors (SSRs). Moreover, like other neuroendocrine molecules, SRIF and SSRs may play a significant role in the progression and neuroendocrine differentiation of human prostate cancer (PCa). However, conflicting results have been reported in the literature on SSR heterogeneity and specific cell localization in PCa. In the present study, using the human ...

Insulin-like growth factor binding protein-2 (IGFBP2) has been demonstrated to be a key mediator of the peripheral actions of leptin, and its deficiency is associated with impaired metabolic function. The metabolic activity of IGFBP2 can be localized to a unique heparin-binding domain (HBD-1) within its structure. AZP-3404 is a 9-amino acid analog of the IGFBP2 HBD-1 that has been demonstrated to increase glucose uptake by differentiated mouse myotubes in vitro, and to increas...

The presence of the truncated somatostatin receptor sst5TMD4 has been correlated with poor prognosis in breast cancer tumorsand its overexpression in breast cancer derived cell lines is associated with increased cell malignancy. The objective of this study was to examine the cellular and molecular mechanisms underlying this association in order to identify new molecular targets for diagnosis, prognosis or therapy of these tumors. Accordingly, in this study, a breast cancer der...