DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for pulmonary arterial hypertension — screening already-approved drugs against its 61-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePulmonary arterial hypertension maps to a 61-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedSunitinibApproved drugapprovedDasatinibApproved drugapprovedImatinibApproved drug
Structures already discussed alongside pulmonary arterial hypertension in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
Pulmonary arterial hypertension remains a disease whose aetiology is not completely clarified, with endothelial dysfunction playing a central role in progression. A 2024 review notes that both genetic predispositions and environmental factors contribute to onset, but it does not report any new trial data, survival figures, or response rates. The review is a summary of existing knowledge, not a source of novel clinical results.
A 2007 review states that treatment has frequently been deficient and empirical, though randomised clinical trials had by then shown useful effects of various drugs. The review does not name specific drugs or give concrete numbers for survival or response. It describes an algorithm for management based on evidence and guidelines, but the evidence base at that time was limited.
A 2013 review reports that in less than two decades multiple targeted treatment options — oral, inhaled, and infused — had been introduced, and that many more were in development. It mentions agents targeting both established and newly identified pathways, and anticipates multiple approvals in the following years. No concrete survival or response rates are provided for any specific therapy.
What is still missing from the literature summarised here is any randomised controlled trial that directly compares repurposed drugs against standard care in pulmonary arterial hypertension, any prospective data on patient stratification by genetic or endothelial biomarkers, and the funding needed to conduct such trials. The reviews are descriptive, not interventional.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2009 · 218 citations
Phosphodiesterase Type 5 Inhibitors for Pulmonary Arterial Hypertension
AbstractA 46-year-old-woman presents with exertional dyspnea and syncope and receives a diagnosis of idiopathic pulmonary arterial hypertension. Treatment with sildenafil is recommended. Sildenafil and tadalafil are phosphodiesterase type 5 inhibitors that ameliorate pulmonary arterial hypertension by increasing levels of cyclic guanosine monophosphate in the smooth-muscle cells of the pulmonary artery.
Impaired endothelium-dependent vasodilation does not initiate the development of sunitinib-associated hypertension
AbstractBACKGROUND: Tyrosine kinase inhibitors targeting angiogenesis have become an important part of the treatment of patients with several types of cancer. One of the most reported side effects of vascular endothelial growth factor receptor (VEGFR)-targeted therapies is hypertension. In this study, we hypothesized that the development of hypertension in patients treated with sunitinib, a multitargeted tyrosine kinase inhibitor, is preceded by reduced endothelium-dependent vasodilation. Moreover, we hypothesized that this endothelial dysfunction is a result of impaired nitric oxide release. METHOD: In a placebo-controlled experiment, we determined vascular responses in isolated mesenteric arteries of rats (n = 26) after 7 days of sunitinib treatment. RESULTS: Sunitinib reduced endothelium-dependent vasodilation, but not endothelium-independent vasodilation. Moreover, we observed that the difference in endothelium-dependent vasodilation between controls and sunitinib-treated animals disappeared in the presence of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist. In patients with metastatic renal cell carcinoma, before and 1 week after start of sunitinib, the endothelium-dependent vasodilator response to intra-arterial acetycholine and the endothelium-independent vasodilator response to intra-arterial sodium nitroprusside was assessed with venous occlusion plethysmography. No changes in forearm blood flow ratios were observed. Mean arterial pressure did significantly increase from 101.9 ± 3.8 to 106.1 ± 2.6 mmHg after 1 week and further to 115.8 (±4.9) mmHg after 2 weeks of treatment. CONCLUSION: In animals, this study confirms that exposure to high concentrations of sunitinib reduces endothelium-dependent vasodilation by reducing endothelial release of nitric oxide. In humans, however, reduced endothelium-dependent vasodilation does not precede the development of hypertension in patients treated with sunitinib.
Journal of Clinical Medicine · 2024 · 19 citations · open access
Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside
AbstractPulmonary arterial hypertension is a complex pathology whose etiology is still not completely well clarified. The pathogenesis of pulmonary arterial hypertension involves different molecular mechanisms, with endothelial dysfunction playing a central role in disease progression. Both individual genetic predispositions and environmental factors seem to contribute to its onset. To further understand the complex relationship between endothelial and pulmonary hypertension and try to contribute to the development of future therapies, we report a comprehensive and updated review on endothelial function in pulmonary arterial hypertension.
Respiratory Care · 2013 · 14 citations · open access
Reversible Pre-Capillary Pulmonary Hypertension Due to Dasatinib
AbstractPulmonary arterial hypertension and secondary pleural effusion have been reported in association with long-term therapy with the multi-tyrosine kinase inhibitor dasatinib, approved for the treatment of chronic myeloid leukemia. Here, we present the case of a 50-year-old man, diagnosed with chronic myeloid leukemia in August 2003, who developed pulmonary arterial hypertension after > 4 years of treatment with dasatinib. The complete remission of pulmonary arterial hypertension following dasatinib discontinuation suggests an etiological role of the drug in its development, although the administration of sildenafil may have played a therapeutic role.
Journal of Oncology Pharmacy Practice · 2018 · 8 citations
Dasatinib-induced pulmonary arterial hypertension – A rare late complication
AbstractDasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.
Current Opinion in Pulmonary Medicine · 2025 · 2 citations
Important negative trials in pulmonary hypertension
AbstractPURPOSE OF REVIEW: The pathobiology of pulmonary arterial hypertension (PAH) is complex and has been characterized by aberrant signalling in diverse pathways, many of which have been explored in recent studies. While some of these studies have demonstrated negative results, nonetheless they provide valuable insights into these drugs and the disease. RECENT FINDINGS: The focus of this article is to provide an overview of recent negative trials in pulmonary hypertension, with a specific focus on PAH. These include recent studies exploring the use of tocilizumab, selonsertib, rodatristat ethyl, anastrazole and dry powder inhalation of imatinib (AV-101). SUMMARY: This article provides an overview of the key learning points from these studies and reinforces the importance of the publication of all trials, irrespective of outcome, so that we can learn from negative studies and prioritize promising therapies and treatment pathways.
Current Respiratory Medicine Reviews · 2007 · 0 citations
Current Treatment of the Pulmonary Arterial Hypertension
AbstractPulmonary arterial hypertension is a feature of a spectrum of diseases that includes elevated pulmonary vascular resistance, induces right ventricular insufficiency and heart failure, and threatens the life. The aetiology and pathogenesis is diverse and associated with elevated morbidity and mortality. Treatment is frequently deficient and empirical. Fortunately, in recent years, randomized clinical trials have shown useful effects of various drugs on pulmonary arterial hypertension. This article reviews the pharmacological and not pharmacological therapeutic options to treat pulmonary arterial hypertension and attempts to provide a proposal of algorithm for its management based upon the evidence and available guidelines for clinical management. Keywords: Pulmonary arterial hypertension, treatment
Current and Emerging Therapies for Pulmonary Arterial Hypertension
AbstractPulmonary arterial hypertension (PAH) is a complex and progressive disease of the pulmonary vasculature that requires targeted medical management for symptom control and improved survival. Use of targeted treatments requires specialized training. In less than 2 decades, multiple targeted treatment options, including oral, inhaled, and infused therapies, have been introduced and many more therapeutic developments are in the pipeline. Agents under investigation include new medications that target established pathways as well as those that target recently identified underlying mechanisms of PAH. In the next few years, multiple agents are anticipated to receive approval and will further shape the evolving treatment domain of PAH.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
