ArticleNature communications2016
Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Pooled it
- Biased Allosteric Modulation in GPCR Drug Discovery.Handbook of experimental pharmacology · 2026Review
- Advances in Parathyroid Hormone-based medicines.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Pseudohypoparathyroidism with normocalcemia: a rare case report from Nepal.Annals of medicine and surgery (2012) · 2025Article
- Structural insights into GPCR signaling activated by peptide ligands: from molecular mechanism to therapeutic application.Experimental & molecular medicine · 2025Review
- Association Between Maternal Vitamin K2 Levels in Late Pregnancy and Newborn Bone Metabolism.Food science & nutrition · 2025Article
- Management of autosomal dominant hypocalcemia type 1: Literature review and clinical practice recommendations.Journal of endocrinological investigation · 2025Review
- Intracellular GPCR modulators enable precision pharmacology.npj drug discovery · 2025Review
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
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- Molecular Mechanisms of PTH/PTHrP Class B GPCR Signaling and Pharmacological Implications.Endocrine reviews · 2023Article
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis.Cancers · 2023Review
- Abnormal changes of bone metabolism markers with age in children with cerebral palsy.Frontiers in pediatrics · 2023Article
- Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Management of Hypoparathyroidism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Precise druggability of the PTH type 1 receptor.Nature chemical biology · 2022Article
- Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.British journal of pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parathyroid hormone (PTH) is essential for calcium homeostasis and its action is mediated by the PTH type 1 receptor (PTHR1), a class B G-protein-coupled receptor. Hypoparathyroidism and osteoporosis can be treated with PTH injections; however, no orally effective PTH analogue is available. Here we show that PCO371 is a novel, orally active small molecule that acts as a full agonist of PTHR1. PCO371 does not affect the PTH type 2 receptor (PTHR2), and analysis using PTHR1-PTHR2 chimeric receptors indicated that Proline 415 of PTHR1 is critical for PCO371-mediated PTHR1 activation. Oral administration of PCO371 to osteopenic rats provokes a significant increase in bone turnover with limited increase in bone mass. In hypocalcemic rats, PCO371 restores serum calcium levels without increasing urinary calcium, and with stronger and longer-lasting effects than PTH injections. These results strongly suggest that PCO371 can provide a new treatment option for PTH-related disorders, including hypoparathyroidism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.