DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for B-cell acute lymphoblastic leukemia — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleB-cell acute lymphoblastic leukemia maps to a 46-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 drug
Structures already discussed alongside b-cell acute lymphoblastic leukemia 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 B cell precursor acute lymphoblastic leukaemia (BCP-ALL) cells, the pre-B cell receptor (pre-BCR) forms transient, short-lived homodimers and higher-order oligomers on the plasma membrane. These homotypic interactions, observed by single-particle tracking with quantum dot-labelled probes, stimulate survival signals including expression of the transcriptional repressor BCL6. Blocking these interactions with inhibitory monovalent antibody fragments (Fabs) specific for the surrogate light chain components of the pre-BCR, or with inhibitors of the tyrosine kinases Lyn and Syk, stopped those survival signals. The same 2016 study reported that preventing homotypic pre-BCR interactions sensitised B cells to chemotherapeutic agents, suggesting that interfering with pre-BCR clustering could improve the efficacy of existing chemotherapy. In contrast, cross-linking pre-BCRs with dimeric galectin-1 produced large, immobile aggregates, a state that was partially reversed by adding lactose.
For Philadelphia chromosome-positive (BCR-ABL1+) ALL in adults, dasatinib has been investigated as a treatment. A 2019 review of clinical studies reported that dasatinib, used alone or in combination with steroids or intensive chemotherapy, is associated with a high complete remission rate. However, mutations at T315 and F317 are associated with dasatinib resistance. Overall toxicity was described as acceptable, with no unexpected toxicity observed. The review noted that it remains unknown whether the antileukaemic effect of dasatinib differs between subsets of BCR-ABL1+ patients, whether it is due solely to inhibition of the fusion protein or to a combined effect on several kinases, and whether dasatinib-containing combinations should be preferred over other emerging strategies such as monoclonal antibodies.
The 2016 study on pre-BCR dynamics did not test any specific drug in patients; it used cell lines and inhibitors in vitro. The 2019 review on dasatinib summarises existing clinical data but does not present new trial results. No direct comparison between targeting pre-BCR homodimers and using dasatinib has been reported. What is still missing are clinical trials that test whether disrupting pre-BCR homotypic interactions (for example with Fabs or kinase inhibitors) improves outcomes in BCP-ALL patients who are not BCR-ABL1+, and whether such an approach can be combined safely with standard chemotherapy. For dasatinib in BCR-ABL1+ ALL, the key missing pieces are prospective data on which patient subsets benefit most, and head-to-head comparisons with newer antibody-based therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Signaling · 2016 · 23 citations · open access
Dynamic pre-BCR homodimers fine-tune autonomous survival signals in B cell precursor acute lymphoblastic leukemia
AbstractThe pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent quantum dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions. Receptor motion was correlated at short separation distances, consistent with the formation of dimers and higher-order oligomers. Repeated encounters between diffusing pre-BCRs appeared to reflect transient co-confinement in plasma membrane domains. In human B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, we showed that frequent, short-lived, homotypic pre-BCR interactions stimulated survival signals, including expression of BCL6, which encodes a transcriptional repressor. These survival signals were blocked by inhibitory monovalent antigen-binding antibody fragments (Fabs) specific for the surrogate light chain components of the pre-BCR or by inhibitors of the tyrosine kinases Lyn and Syk. For comparison, we evaluated pre-BCR aggregation mediated by dimeric galectin-1, which has binding sites for carbohydrate and for the surrogate light chain λ5 component. Galectin-1 binding resulted in the formation of large, highly immobile pre-BCR aggregates, which was partially relieved by the addition of lactose to prevent the cross-linking of galectin-BCR complexes to other glycosylated membrane components. Analysis of the pre-BCR and its signaling partners suggested that they could be potential targets for combination therapy in BCP-ALL.
Expert Opinion on Investigational Drugs · 2019 · 20 citations
Dasatinib as an investigational drug for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults
AbstractIntroduction: Acute lymphoblastic leukemia (ALL) with BCR-ABL1 translocation is an aggressive malignancy that is usually treated with intensive chemotherapy with the possibility of allogeneic stem cell transplantation. The encoded fusion protein may be important for leukemogenesis; clinical studies show that dasatinib has an antileukemic effect in combination with steroids alone or intensive chemotherapy.Areas covered: Relevant publications were identified through literature searches (the used terms being acute lymphoblastic leukemia plus dasatinib) in the PubMed database. We searched for original articles and reviews describing the pharmacology and clinical use of dasatinib in ALL with BCR-ABL1. The mechanism of action, pharmacology and clinical study findings are examined.Expert opinion: Dasatinib is associated with a high complete remission rate in ALL when used alone and in combination with steroids or intensive chemotherapy. However, mutations at T315 and F317 are associated with dasatinib resistance. Overall toxicity has been acceptable in these studies and no unexpected toxicity was observed. It is not known whether the antileukemic effect of dasatinib differs between subsets of BCR-ABL1+ patients or is attributed to inhibition of the fusion protein alone, or a combined effect on several kinases, and whether dasatinib-containing combination treatment should be preferred in these patients instead of other emerging strategies, e.g. monoclonal antibodies.Trial registration: ClinicalTrials.gov identifier: NCT02744768.Trial registration: ClinicalTrials.gov identifier: NCT02143414.Trial registration: ClinicalTrials.gov identifier: NCT02494882.Trial registration: ClinicalTrials.gov identifier: NCT02420717.Trial registration: ClinicalTrials.gov identifier: NCT02815059.Trial registration: ClinicalTrials.gov identifier: NCT00103701.Trial registration: ClinicalTrials.gov identifier: NCT00337454.Trial registration: ClinicalTrials.gov identifier: NCT00816283.Trial registration: ClinicalTrials.gov identifier: NCT03564470.Trial registration: ClinicalTrials.gov identifier: NCT03414450.Trial registration: ClinicalTrials.gov identifier: NCT01256398.Trial registration: ClinicalTrials.gov identifier: NCT00792948.Trial registration: ClinicalTrials.gov identifier: NCT00036738.Trial registration: ClinicalTrials.gov identifier: NCT01883219.Trial registration: ClinicalTrials.gov identifier: NCT03624530.Trial registration: ClinicalTrials.gov identifier: NCT01643603.Trial registration: ClinicalTrials.gov identifier: NCT01643603.Trial registration: ClinicalTrials.gov identifier: NCT02888990.Trial registration: ClinicalTrials.gov identifier: NCT02888977.
<i>Science Signaling</i> Podcast for 29 November 2016: Pre-B cell receptor signaling in leukemia
AbstractThis Podcast features an interview with Bridget Wilson, author of a Research Article that appears in the 29 November 2016 issue of Science Signaling, about pre-B cell receptor (pre-BCR) signaling in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Signaling through the pre-BCR, an immature form of the BCR, promotes the survival of B cell progenitors and has been implicated in the pathology of BCP-ALL. Erasmus et al found that pre-BCRs formed transient homomeric complexes that correlated with pro-survival signaling. Preventing homotypic interactions between pre-BCRs sensitized B cells to chemotherapeutic agents, suggesting that interfering with such interactions may improve the efficacy of existing chemotherapies for BCP-ALL.Listen to Podcast.
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.
