ArticleAmerican journal of respiratory cell and molecular biology2020
KD025 Shifts Pulmonary Endothelial Cell Bioenergetics and Decreases Baseline Lung Permeability.
Article in American journal of respiratory cell and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 15 citations in OpenAlex.
- Selective ROCK2 inhibition reduces microvascular obstruction but does not reduce myocardial infarction after ischaemia and reperfusion.Journal of molecular and cellular cardiology plus · 2026Article
- ROCK 2 inhibition with belumosudil for the treatment of chronic graft-versus-host disease: a narrative review.Therapeutic advances in hematology · 2025Review
- New perspectives on the progression of pulmonary fibrosis: the cascade from aberrant microvascular endothelial cell activation to fibrosis.Frontiers in medicine · 2025Review
- Unlocking the secrets of glucose metabolism reprogramming: the role in pulmonary diseases.Frontiers in pharmacology · 2025Review
- Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF).Expert review of clinical pharmacology · 2024Review
- Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung.International journal of molecular sciences · 2023Review
- PFKFB3 Inhibits Fructose Metabolism in Pulmonary Microvascular Endothelial Cells.American journal of respiratory cell and molecular biology · 2023Article
- Roles of the RhoA-ROCK Signaling Pathway in the Endothelial HACS omega · 2022Article
- Metabolic reprogramming of pulmonary fibrosis.Frontiers in pharmacology · 2022Review
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Belumosudil: First Approval.Drugs · 2021Review
- KD025, an anti-adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2-overexpressing leukemia cells.Oncology letters · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
KD025 is a ROCK2 inhibitor currently being tested in clinical trials for the treatment of fibrotic lung diseases. The therapeutic effects of KD025 are partly due to its inhibition of profibrotic pathways and fat metabolism. However, whether KD025 affects pulmonary microvascular endothelial cell (PMVEC) function is unknown, despite evidence that alveolar-capillary membrane disruption constitutes major causes of death in fibrotic lung diseases. We hypothesized that KD025 regulates PMVEC metabolism, pH, migration, and survival, a series of interrelated functional characteristics that determine pulmonary barrier integrity. We used PMVECs isolated from Sprague Dawley rats. KD025 dose-dependently decreased lactate production and glucose consumption. The inhibitory effect of KD025 was more potent compared with other metabolic modifiers, including 2-deoxy-glucose, extracellular acidosis, dichloroacetate, and remogliflozin. Interestingly, KD025 increased oxidative phosphorylation, whereas 2-deoxy-glucose did not. KD025 also decreased intracellular pH and induced a compensatory increase in anion exchanger 2. KD025 inhibited PMVEC migration, but fasudil (nonspecific ROCK inhibitor) did not. We tested endothelial permeability
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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.