DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Richter syndrome — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRichter syndrome maps to a 44-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 richter syndrome 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
mitogen-activated protein kinase 1 (MAPK1) — MAPK1 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 2~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AOJ · 1.12 Å · ligand 1-[(2~{S})-2-(5-methyl-3-pyridin-4-yl-1~{H}-pyrazol-4-yl)pyrrolidin-1-yl]propan-1-one (N8L). Experimental structure, not a prediction.
What the evidence adds up to
Richter syndrome occurs in up to 15% of patients with chronic lymphocytic leukaemia and is usually a transformation to diffuse large B-cell lymphoma. In a genomic analysis of 59 RS cases, 28 CLL phases preceding RS, 315 CLL cases, and 127 de novo DLBCL cases, RS showed genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and CDKN2A was present in about half of RS cases and affected patient outcome. A second subgroup, comprising one third of cases, was characterised by trisomy 12. The CLL phase before RS did not show a general increase in genomic complexity compared with untransformed CLL, but had clear differences in the frequency of specific genetic lesions.
A phase II trial of CHOP-21 plus ofatumumab induction followed by 12 months of ofatumumab maintenance enrolled 43 patients, of whom 37 were evaluable. Seventy-three per cent were over 60 years old, and over half had received prior fludarabine and cyclophosphamide. The overall response rate at six cycles was 46% (complete response 27%, partial response 19%). Median progression-free survival was 6.2 months (95% CI 4.9–14.0 months) and median overall survival was 11.4 months (95% CI 6.4–25.6 months). Treatment-naïve and TP53-intact patients had better outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections occurred; there were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, but only one responded adequately to proceed to allogeneic transplantation. The authors concluded that CHOP-O provides minimal benefit beyond CHOP plus rituximab and that standard immunochemotherapy remains wholly inadequate for unselected RS.
A single case report described a 53-year-old man with heavily pretreated, refractory Richter syndrome who received rituximab and ibrutinib and achieved a significant response after one month. Two case reports from 1987 described radiographic manifestations of RS including hepatosplenomegaly, diffuse marked adenopathy, and skeletal involvement.
What is still missing are multinational trials incorporating novel agents, which the phase II authors stated are urgently needed. No randomised controlled trial has established a standard therapy for RS. Patient stratification by TP53 status and prior treatment history may be necessary to interpret future results, but no validated biomarker-driven trial design has been tested.
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 · 2013 · 249 citations · open access
Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome
AbstractRichter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
British Journal of Haematology · 2016 · 67 citations
<scp>NCRI</scp> phase <scp>II</scp> study of <scp>CHOP</scp> in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome
AbstractRichter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 6·2 months (95% confidence interval [CI] 4·9-14·0 months) and median OS was 11·4 months (95% CI 6·4-25·6 months). Treatment-naïve and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.
Journal of Computer Assisted Tomography · 1987 · 9 citations
CT Manifestations of Richter Syndrome
AbstractRichter syndrome is an uncommon complication of chronic lymphocytic leukemia characterized by its transformation into diffuse histiocytic lymphoma. We present two documented cases of Richter syndrome and its radiographic manifestations, which have not previously been reported. These include hepatosplenomegaly, diffuse marked adenopathy, and involvement of the skeletal system. The diagnosis of Richter syndrome should be suggested when these radiographic findings occur with chronic lymphocytic leukemia.
Clinical Case Reports · 2014 · 0 citations · open access
Characterization of garlic skin and its evaluation as biomaterial
AbstractWe report a 53-year-old man diagnosed with Richter syndrome. He was heavily pretreated and was refractory to prior therapy. He received rituximab and ibrutinib, and achieved a significant response after 1 month of therapy. Our case illustrates the importance of investigation of rituximab and ibrutinib in Richter's syndrome.
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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