ArticleJACC. Basic to translational science2024
Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression.
Article in JACC. Basic to translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Serotonin in Cardiovascular Disease: From Pathophysiological Insights to Clinical Utility.Diagnostics (Basel, Switzerland) · 2026Review
- Plasma Tryptophan Hydroxylase 1 Activity-related Metabolic Markers and Stroke Risk: A Nested Case-control Study.Translational stroke research · 2026Article
- Neonatal pulmonary vascular remodeling induced by increased blood flow is associated with an antiviral-like immune signature.Frontiers in immunology · 2026Article
- 5-HT regulates resistance to aumolertinib by attenuating ferroptosis in lung adenocarcinoma.EMBO molecular medicine · 2025Article
- Selectivity and Safety Characterization of a Xanthine-Imidazothiazole Lead Structure: a Novel Tryptophan Hydroxylase Inhibitor of Peripheral Serotonin Synthesis.ACS pharmacology & translational science · 2025Article
- Inhibiting Serotonin Synthesis for the Treatment of Pulmonary Arterial Hypertension.Pulmonary circulation · 2025Article
- Zhi-zi-chi decoction exerts hypnotic effect through gut-brain axis modulation in insomnia mice.Frontiers in microbiology · 2025Article
- Selective Inhibition of Peripheral Serotonin Synthesis in Pulmonary Hypertension.JACC. Basic to translational science · 2024Article
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Authors and funding
9 authors.
Funding
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Abstract
The serotonin pathway has long been proposed as a promising target for pulmonary arterial hypertension (PAH)-a progressive and uncurable disease. We developed a highly specific inhibitor of the serotonin synthesizing enzyme tryptophan hydroxylase 1 (TPH1), TPT-001 (TPHi). In this study, the authors sought to treat severe PAH in the Sugen/hypoxia (SuHx) rat model with the oral TPHi TPT-001. Male Sprague Dawley rats were divided into 3 groups: 1) ConNx, control animals; 2) SuHx, injected subcutaneously with SU5416 and exposed to chronic hypoxia for 3 weeks, followed by 6 weeks in room air; and 3) SuHx+TPHi, SuHx animals treated orally with TPHi for 5 weeks. Closed-chest right- and left heart catheterization and echocardiography were performed. Lungs were subject to histologic and mRNA sequencing analyses. Compared with SuHx-exposed rats, which developed severe PAH and right ventricular (RV) dysfunction, TPHi-treated SuHx rats had greatly lowered RV systolic (mean ± SEM: 41 ± 2.3 mm Hg vs 86 ± 6.5 mm Hg;
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