DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Hypereosinophilic syndrome — screening already-approved drugs against its 9-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypereosinophilic syndrome maps to a 9-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
approvedDasatinibApproved drugapprovedImatinibApproved drug
Structures already discussed alongside hypereosinophilic syndrome 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
In a 2005 study, nine patients with hypereosinophilic syndrome and end-organ involvement received a combination of 2-chlorodeoxyadenosine and cytarabine. Five patients (55%) achieved a complete remission; one required two courses. Median disease-free survival among those who reached remission was 26 months, and median overall survival from diagnosis was 44 months. Febrile neutropenia occurred in 28% of the 14 courses given, and median time to recovery from neutropenia and thrombocytopenia was 17 and 39 days respectively. The authors concluded the regimen had activity.
A 2009 report described two paediatric cases of hypereosinophilic syndrome in which steroid therapy was effective. No further details of sample size or duration of response were provided.
A 2013 review noted that idiopathic hypereosinophilic syndrome remained the prevalent diagnosis in patients with persistent eosinophilia. Imatinib-sensitive fusion proteins (PDGFRA, PDGFRB, FGFR1, JAK-2, FLT3) had been identified in only 10–20% of patients with persistent primary hypereosinophilia. Patients whose hypereosinophilic myeloproliferative neoplasms carried PDGFRA or PDGFRB fusions were responsive to imatinib. The review emphasised that a key challenge was to identify new targets and reduce the number of patients classified as having idiopathic disease.
A 2015 case report described a patient with hypereosinophilic syndrome and PDGFRB rearrangement who developed resistance to imatinib. Salvage therapy with dasatinib, methylprednisolone and hydroxyurea was administered. The abstract does not report whether this combination produced a response or for how long.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 2005 · 25 citations · open access
2‐Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic hypereosinophilic syndrome
AbstractBACKGROUND: Hypereosinophilic syndrome (HES) is a rare, disabling, and incurable disease. In this study, a combination of 2-chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (ara-C) chemotherapy was evaluated in patients with HES. METHODS: Nine patients with HES were treated with ara-C (1 g/m(2)) given intravenously over 2 hours at 0 hours, 48 hours, 72 hours, 96 hours, and 120 hours; and 2-CdA (12 mg/m(2) per day) was given as a continuous intravenous infusion over 5 days starting at 24 hours. A second course of the same therapy was administered in patients who had a response. RESULTS: All patients had signs and symptoms of end-organ involvement. The median time from diagnosis to therapy was 25 months. Seven patients had received prior therapies. Five patients (55%) achieved a complete remission (CR), 1 after receiving 2 courses of therapy. Elimination of eosinophilia was accompanied by the resolution of symptoms. The median disease-free survival and overall survival after the diagnosis for patients who achieved CR was 26 months and 44 months, respectively. Treatment was tolerated well. Febrile neutropenia occurred in 28% of the 14 courses that were given. The median time to recovery from neutropenia and thrombocytopenia was 17 days and 39 days, respectively. CONCLUSIONS: The combined 2-CdA and ara-C chemotherapy regimen had activity in patients with HES.
Pediatric Hematology and Oncology · 2009 · 11 citations
HYPEREOSINOPHILIC SYNDROME IN CHILDHOOD: Clinical and Molecular Features of Two Cases
AbstractHypereosinophilic syndrome (HES) represents a heterogeneous group of diseases, some of which are being clarified by recent advances in molecular genetics. It is very rare in children. Uncertainties in classification and lack of prospective studies make therapeutic decisions difficult. The authors report two cases of HES in which steroid therapy was effective.
Current Opinion in Hematology · 2013 · 7 citations
Eosinophilic myeloid neoplasms
AbstractPURPOSE OF REVIEW: In 2012, idiopathic hypereosinophilic syndrome (HES) is still the prevalent diagnosis in patients with persistent eosinophilia, in which a primary or secondary cause of eosinophilia has not been identified. HES is considered a provisional diagnosis until a primary or secondary cause of hypereosinophilia is established. The discovery of imatinib-sensitive fusion proteins in a subset of patients with hypereosinophilia has changed the way we approach the diagnosis and treatment of eosinophilic myeloid neoplasms [eosinophilic myeloproliferative neoplasms (MPNs)]. Despite the recent diagnostic developments, diagnosis of hypereosinophilic MPN is only made in 10-20% of patients with persistent primary hypereosinophilia. RECENT FINDINGS: In 2008 the World Health Organization (WHO) established a semi-molecular classification of hypereosinophilic MPNs. The discovery of PDGFRA, PDGFRB, FGFR1, JAK-2, and FLT3 fusion proteins in patients with eosinophilic MPNs provide opportunities for targeted therapy. Patients with hypereosinophilic MPNs associated with PDGFRA and PDGFRB fusion genes are responsive to imatinib. SUMMARY: Ongoing research continues to expand our understanding of the pathophysiology of persistent primary hypereosinophilia and clarify the boundaries between some of these disorders. A key challenge is to identify new targets for therapy and limit the number of patients who are classified as having HES.
Leukemia Research Reports · 2021 · 2 citations · open access
Eosinophilia characterized by a rare CCT6B mutation and responsive to tyrosine kinase inhibition: Case report and literature review
AbstractHypereosinophilic syndrome is a rare disorder arising from neoplastic, or idiopathic causes. The availability of NGS panels has increasingly identified rare mutations as underlying pathogenic events and have led to reclassification of cases of idiopathic hypereosinophilic syndrome as chronic eosinophilic leukemia(CEL). In this report, we describe a case of a young man with hypereosinophilia whose disease initially did not fit the WHO criteria for CEL but harbored a rare mutation in CCT6B gene. We report our experience in successfully treating this patient with multiple tyrosine kinase inhibitors and provide literature review of this rare entity including potential treatment strategies.
Journal of Cancer Research and Practice · 2015 · 1 citations · open access
Salvage therapy of imatinib-resistant hypereosinophilic syndrome with PDGFRB rearrangement
AbstractHypereosinophilic syndrome (HES) has generally been defined as a peripheral blood eosinophil count greater than 1500/mm3 and may be associated with tissue damage. Imatinib is customarily used as the first-line therapy for HES with gene abnormalities, such as PDGFRA or PDGFRB. We presented a case where the patient was diagnosed with HES, with PDGFRB rearrangement. The patient began an imatinib regimen after diagnosis and then developed resistance to imatinib. The combination of dasatinib, methylprednisolone and hydroxyurea was administered to the patient as the salvage therapy.
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.
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