ArticleCPT: pharmacometrics & systems pharmacology2015
A Systems Pharmacology Model of Erythropoiesis in Mice Induced by Small Molecule Inhibitor of Prolyl Hydroxylase Enzymes.
Article in CPT: pharmacometrics & systems pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed, 4 citations in OpenAlex.
- Quantitative systems pharmacology model of erythropoiesis to simulate therapies targeting anemia due to chronic kidney disease.Frontiers in pharmacology · 2023Article
- Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat.Clinical pharmacokinetics · 2022Review
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mammalian erythropoiesis is a conserved process tightly controlled by the hypoxia-inducible factor (HIF1) pathway. In this study, a small molecule inhibitor (PHI-1) of prolyl-hydroxylase-2 (PHD2) enzyme involved in regulating HIF1α levels was orally administered to male BALB/c mice at 10 and 30 mg/kg. A systems pharmacology model was developed based on the measured PHI-1 plasma exposures, kidney HIF1α, kidney erythropoietin (EPO) mRNA, plasma EPO, reticulocyte counts, red blood cells, and hemoglobin levels. The model fit resulted in the estimation of drug potency (IC50: 1.7μM), and systems parameters such as EPO mRNA turnover (kdeg_EPOmRNA: 0.43 hr(-1)) and mean lifespan of reticulocytes (Tr : 81 hours). The model correctly described the observed 30-40-fold increase in kidney HIF1α protein, ∼1,000 fold increase in EPO mRNA and 2-3-fold increase in the reticulocytes at 30 mg/kg. This study presents the first parsimonious systems model of erythropoiesis to quantitatively describe the in vivo effects of PHD2 inhibition.
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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.