DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for acute erythroleukemia — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcute erythroleukemia maps to a 1-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
No approved-drug candidate for acute erythroleukemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
erb-b2 receptor tyrosine kinase 3 (ERBB3) — ERBB3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7MN5 · 2.93 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Three children with acute erythroleukemia were studied for chromosomal changes in 1968. Two had persistently normal karyotypes despite relapse. The third had a missing C chromosome with 45/46 mosaicism in the bone marrow and a dichotomy between blood (modal count 46) and bone marrow (modal count 45); these abnormalities were evident only during relapse. After partial remission induced with cytosine arabinoside, all subsequent analyses were normal. This was the third reported case of a child with erythroleukemia showing aneuploidy in the C group of chromosomes.
A 53-year-old male developed acute erythroleukemia three years after renal transplantation in a 1979 report. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognised. The authors noted that azathioprine has been associated with chromosome abnormalities and suggested that chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.
In 2024, a series of compounds synthesised from the carbazole alkaloid calothrixin B were tested against HEL cells, a human erythroleukemia cell line. One compound, H-107, showed an IC50 value of 3.63 ± 0.33 μM. H-107 induced apoptosis by damaging mitochondria and activating the caspase cascade, and arrested HEL cells in the G0/G1 phase. It downregulated protein levels of Ras, p-Raf, p-MEK, p-ERK and c-Myc. Pretreatment with the ERK inhibitor U0126 increased H-107-induced apoptosis. In erythroleukemia mice, H-107 promoted erythroid differentiation into mature erythrocytes and activated immune cells.
These findings come from a single cell-line study and a mouse model. No human trial of H-107 has been reported. What is missing is any clinical testing in patients, any data on survival or response rates in humans, and any understanding of whether the chromosomal heterogeneity seen in the 1968 and 1979 reports would affect response to this compound. Money for a phase 1 trial, a trial design that accounts for patient stratification by karyotype, and replication by independent groups are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 1968 · 24 citations · open access
Brief Report: A Cytogenetic Study of Acute Erythroleukemia in Children
AbstractAbstract Three children with acute erythroleukemia were studied for chromosomal changes. Two of them had persistently normal karyotypes despite relapse. The third patient was missing a C chromosome, and had 45/46 mosaicism in the bone marrow and a dichotomy between blood (mode of 46) and bone marrow (mode of 45). All of these abnormalities were only evident when he was in relapse. Following partial remission induced with cytosine arabinoside, all subsequent analyses were normal. This is the third case reported of a child with erythroleukemia with aneuploidy in the C group of the chromosomes.
AbstractA 53-year-old male developed acute erythroleukemia three years after renal transplantation. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognized. Azathioprine has been associated with chromosome abnormalities. The chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.
Calothrixin B derivatives induce apoptosis and cell cycle arrest on HEL cells through the ERK/Ras/Raf/MEK pathway
AbstractBACKGROUND: Acute erythroleukemia (AEL) is acute myeloid leukemia characterized by malignant erythroid proliferation. AEL has a low survival rate, which has seriously threatened the health of older adults. Calothrixin B is a carbazole alkaloid isolated from the cyanobacteria Calothrix and exhibits anti-cancer activity. To discover more potential anti-erythroleukemia compounds, we used calothrixin B as the structural skeleton to synthesize a series of new compounds. METHODS: In the cell culture model, we evaluated apoptosis and cell cycle arrest using MTT assay, flow cytometry analysis, JC-1 staining, Hoechst 33258 staining, and Western blot. Additionally, assessing the curative effect in the animal model included observation of the spleen, HE staining, flow cytometry analysis, and detection of serum biochemical indexes. RESULTS: value of 3.63 ± 0.33 μM. H-107 induced apoptosis of HEL cells by damaging mitochondria and activating the caspase cascade and arrested HEL cells in the G0/G1 phase. Furthermore, H-107 downregulated the protein levels Ras, p-Raf, p-MEK, p-ERK and c-Myc. Pretreatment with ERK inhibitor (U0126) increased H-107-induced apoptosis. Thus, H-107 inhibited the proliferation of HEL cells by the ERK /Ras/Raf/MEK signal pathways. Interestingly, H-107 promoted erythroid differentiation into the maturation of erythrocytes and effectively activated the immune cells in erythroleukemia mice. CONCLUSION: Overall, our findings suggest that H-107 can potentially be a novel chemotherapy for erythroleukemia.
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.
