ArticleCPT: pharmacometrics & systems pharmacology2017
Translational Modeling of Drug-Induced Myelosuppression and Effect of Pretreatment Myelosuppression for AZD5153, a Selective BRD4 Inhibitor.
Article in CPT: pharmacometrics & systems pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Model-Based Prediction of Clinically Relevant Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation.Clinical pharmacology and therapeutics · 2025Article
- Application of Mechanistic Mathematical Modeling to Toxicology: Quantitative Systems Toxicology (QST).Handbook of experimental pharmacology · 2025Review
- First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.Molecular cancer therapeutics · 2023Article
- The evolving role of investigative toxicology in the pharmaceutical industry.Nature reviews. Drug discovery · 2023Review
- PROTAC'ing oncoproteins: targeted protein degradation for cancer therapy.Molecular cancer · 2023Review
- Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study.Clinical and translational medicine · 2022Article
- Using thrombocytopenia modeling to investigate the mechanisms underlying platelet depletion induced by pan-proteasome inhibitors.CPT: pharmacometrics & systems pharmacology · 2022Article
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Importance of Stability Analysis When Using Nonlinear Semimechanistic Models to Describe Drug-Induced Hematotoxicity.CPT: pharmacometrics & systems pharmacology · 2020Article
- An in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias.PLoS computational biology · 2020Article
- Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.CPT: pharmacometrics & systems pharmacology · 2019Article
- Bromodomains: a new target class for drug development.Nature reviews. Drug discovery · 2019Review
- BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor.International journal of biological sciences · 2019Article
- Impact of a five-dimensional framework on R&D productivity at AstraZeneca.Nature reviews. Drug discovery · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this work, we evaluate the potential risk of thrombocytopenia in man for a BRD4 inhibitor, AZD5153, based on the platelet count decreases from a Han Wistar rat study. The effects in rat were modeled and used to make clinical predictions for human populations with healthy baseline blood counts. At doses >10 mg, a dose-dependent effect on circulating platelets is expected, with similar predicted changes for both q.d. and b.i.d. dose schedules. These results suggest that at predicted efficacious doses, AZD5153 is likely to have some reductions in the clinical platelet counts, but within the normal range at projected efficacious doses. The model was then extended to incorporate preexisting myelosuppression where bone marrow function is inhibited by acute myeloid leukemia. Under these conditions, duration of platelet count recovery has the potential to be prolonged due to drug-induced myelosuppression.
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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.