Oncofusion

start / graph / absence-nothing-has-ever-been-measured-in-parathyroid-under-a-menin-inhibitor

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q127-pi-dimensions-at-the-centre

Absence: the tissue with the clinical signal is the one tissue nobody has put under a menin inhibitor and measured - one record in the whole literature, and it is a review

also called no parathyroid pharmacology for menin inhibitors

A third of patients on the approved menin drug show a rise in parathyroid hormone. Nobody has ever taken parathyroid tissue, given it the drug, and measured what happens inside the cells. The only paper that mentions both the drug class and the gland is a review article.

The same thing, for a scientist

Bounded PubMed search, 2026-09-23: the twelve-name menin-inhibitor clause AND parathyroid returns 1 record, and that record is a 2025 review [E2]. The same drug clause returns 3 records with pituitary and 3 with an islet clause, and the informative ones are beta-cell replication studies. So while the endocrine transcript prediction has been tested in beta cells [E3], the tissue where the clinical signal actually is - intact PTH increased in 34% of 241 patients on the revumenib label - has NO experimental measurement of any kind under a menin inhibitor: no transcript, no chromatin, no proliferation, no secretion. GEO returns one series pairing menin with an endocrine tissue and it is a GENETIC Men1 deletion in islets, not a drug.

Go deeper
The queries, with the counts and the translations PubMed actually ran

Run with scripts/pubmed_safe.py on 2026-09-23. One [tiab] tag per term throughout, so rule 94's grouped-tag defect does not apply; the returned translations confirm every term kept [Title/Abstract].

queryn
drug-name clause alone (control)348
parathyroid[tiab] alone (control)58,162
CDK-inhibitor clause alone (control)17,196
menin[tiab] AND CDK-inhibitor clause (bare-operand control, rule 72)57
drug clause AND CDK-inhibitor clause2
drug clause AND (parathyroid OR pituitary OR islet)3
drug clause AND CDK clause AND endocrine clause1
drug clause AND (parathyroid OR chief cell)1

Drug-name clause, verbatim: revumenib[tiab] OR ziftomenib[tiab] OR bleximenib[tiab] OR "VTP-50469"[tiab] OR VTP50469[tiab] OR "MI-503"[tiab] OR "MI-2"[tiab] OR "MI-3454"[tiab] OR "SNDX-5613"[tiab] OR "KO-539"[tiab] OR "menin inhibitor"[tiab] OR "menin inhibitors"[tiab] OR "menin inhibition"[tiab] - singular, plural and nominalisation all present, and both the hyphenated and unhyphenated forms of VTP-50469, per rule 72.

The controls are large and the bare-operand control returns 57, so the small numbers are not an instrument failure. The one parathyroid record is PMID 40152985, a review 2.

What the counts are NOT saying

This absence was very nearly written one claim wider, and the wider version would have been false. The first draft of this beat was going to record no CDK-inhibitor readout under a menin inhibitor in any endocrine tissue. Running the three-way query as a control, expecting zero, returned PMID 32646642, in which a menin-MLL inhibitor down-regulates CDKN1A, CDKN1B and CDKN2C in primary human beta cells 3 - and that paper was already cited twice in this graph.

So: the endocrine CDK-inhibitor question has been answered once, in beta cells, in the predicted direction. What remains absent is parathyroid, and only parathyroid.

The archive check, and why the class is never-measured

GEO (db=gds), 2026-09-23:

  • (menin inhibitor OR revumenib OR ziftomenib OR VTP-50469 OR SNDX-5613) AND (parathyroid OR pituitary OR islet) -> 1 series, GSE26978, which is expression profiling of islets from Men1fl/fl RIP-Cre mice - a genetic deletion, not a drug.
  • (menin inhibitor OR revumenib OR VTP-50469) AND H3K4 -> 0 series.
  • menin AND parathyroid -> 2 series, GSE64412 (human MEN1 parathyroid tumour methylation) and GSE29674 (young Men1 heterozygote islets) - both genetic, neither pharmacological.

No deposited dataset exists in which parathyroid tissue was exposed to a menin inhibitor, so there is nothing to reanalyse. Closing this needs wet work, which is why the class is never-measured rather than measured-not-analysed. The genetic analogues are deposited and unanalysed for the chromatin question, which is a separate and much cheaper absence.

Facts and figures
absence classnever-measured
absence class noteBoth arms checked. Literature: 1 record for the twelve-name menin-inhibitor clause AND parathyroid, and it is a review (PMID 40152985); controls 348 and 58,162, bare-operand control 57, so the small count is not an instrument failure. Archive: GEO returns no series in which parathyroid tissue was exposed to a menin inhibitor; the three menin-plus-endocrine series that exist (GSE26978, GSE64412, GSE29674) are all GENETIC Men1 perturbations. There is therefore no deposited data to reanalyse and closing this needs new material, which is what never-measured means. The adjacent and much cheaper absence - the chromatin question has never been asked of the deposited genetic series - would be measured-not-analysed and is recorded in open_questions rather than claimed here.
the absent measurementany experimental readout in parathyroid tissue under any menin inhibitor: transcript, chromatin, proliferation or PTH secretion
why it mattersintact parathyroid hormone increased in 34% of 241 patients on the revumenib US label at a median exposure of 2.5 months (gene-men1 E6). The clinical signal is in parathyroid and the preclinical work is in islet and marrow.
what was NOT absent and was nearly claimedthe endocrine CDK-inhibitor readout under a menin inhibitor. PMID 32646642 measures it in human beta cells, in the predicted direction, and was already cited twice in this corpus. The wider absence was drafted and withdrawn before it was written.
bounded queries fileanalyses/q127-the-pi-dimensions-at-the-centre/bounded-queries.json
scriptscripts/pubmed_safe.py (esearch) plus NCBI esearch db=gds; query strings, counts and returned querytranslations persisted to analyses/q127-the-pi-dimensions-at-the-centre/bounded-queries.json
statusrun
result summary1 PubMed record for a twelve-name menin-inhibitor clause AND parathyroid, and it is a review; 0 GEO series in which parathyroid was exposed to a menin inhibitor. Controls 348 (drug clause), 58,162 (parathyroid), 57 (bare-operand menin AND CDK clause). The wider absence originally drafted - no endocrine CDK-inhibitor readout under a menin inhibitor - is FALSE and was withdrawn before writing: PMID 32646642 measures it in human beta cells.
name list used
[
  "revumenib",
  "ziftomenib",
  "bleximenib",
  "VTP-50469",
  "VTP50469",
  "MI-503",
  "MI-2",
  "MI-3454",
  "SNDX-5613",
  "KO-539",
  "menin inhibitor",
  "menin inhibitors",
  "menin inhibition"
]
names not tried
[
  "enzomenib",
  "DSP-5336",
  "BMF-219 / covalent menin inhibitors",
  "JNJ-75276617 spelled as a code rather than as bleximenib",
  "any compound published only under an internal code"
]
inputs
[
  "PubMed esearch db=pubmed 2026-09-23",
  "NCBI GEO esearch db=gds 2026-09-23"
]
How this could bite us back
  • The drug has a labelled endocrine adverse reaction in a tissue that has never been studied experimentally under the drug. Any mechanistic account of that adverse reaction in this graph, including the one proposed in hyp-one-mark-two-opposite-cell-state-programmes, is extrapolation from islet and osteosarcoma - and those two disagree in sign.
Still open
  1. Has the chromatin question been asked of the deposited genetic series? GSE26978 profiles islets from Men1-deleted mice and its own GEO summary says the menin complex promotes H3K4me3 at homeobox genes AND CDK inhibitor genes. Nobody in this corpus has opened it. That absence is measured-not-analysed and costs compute, not wet work.
  2. Does enzomenib or any covalent menin inhibitor have a parathyroid readout? The name list above is missing at least four compound names and the absence is only as strong as the list.
  3. Do the revumenib and ziftomenib nonclinical packages contain parathyroid histopathology? Regulatory review documents are outside PubMed entirely and this graph has previously found decisive facts in them.
Every source behind this entry (4)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    A bounded PubMed search on 2026-09-23 combining a twelve-name menin-inhibitor clause with a parathyroid clause returns 1 record, against control counts of 348 for the drug clause alone and 58,162 for parathyroid alone, and 57 for the bare-operand control menin[tiab] AND the CDK-inhibitor clause.

    NCBI E-utilities esearch, db=pubmed, executed via scripts/pubmed_safe.py; full query strings, counts and returned querytranslations persisted · Q127 beat, oncofusion knowledge graph · analyses/q127-the-pi-dimensions-at-the-centre/bounded-queries.json 2026
    What this evidence cannot show

    Bounded by TITLES AND ABSTRACTS only (rule 80). A parathyroid measurement buried in a supplementary figure of a leukaemia paper would be invisible to this and no full texts were opened. The name list is the limiting factor and is quoted in full in this entry so a reader can judge it; compounds not on the list - and any compound published under a code this beat did not know - are not covered. No preprint server was searched.

    Evidence that argues against this (1)
    • A literature bound is bounded by TITLES AND ABSTRACTS. The founding endocrine chromatin experiment for this axis reports its p27 and p18 ChIP in figures, and an equivalent parathyroid panel inside a paper about something else would be invisible to every query in this table. The absence is a statement about what has been REPORTED IN AN ABSTRACT, not about what has been measured. Karnik SK et al. 2005
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.review

    The single record returned by the menin-inhibitor clause AND parathyroid is a 2025 review of menin biology and menin-inhibitor development, not a primary measurement in parathyroid tissue.

    Menin: from molecular insights to clinical impact. · Brown MR, Soto-Feliciano YM · Epigenomics 2025
    PMID 40152985DOI
    What this evidence cannot show

    Review, included here only to identify what the single hit is; abstract read, full text not opened, so if it contains an unpublished parathyroid observation this entry would miss it. NOT CITED anywhere in this corpus before 2026-09-23, which is itself notable for a 2025 review of exactly this target.

    Evidence that argues against this (1)
    • A 2025 review of exactly this target is the most likely place for an unpublished or conference-only parathyroid observation to be summarised, and only its abstract was read here. If the review's body cites a parathyroid experiment, this absence is wrong and the review is where it would be found. Brown MR et al. 2025
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In primary human pancreatic beta cells the menin-MLL interaction inhibitor MI-2 with TGF-beta inhibitors synergistically increased replication, cooperating through down-regulation of CDKN1A, CDKN1B and CDKN2C - so the endocrine CDK-inhibitor question is not unmeasured in general, only in parathyroid.

    Combined inhibition of menin-MLL interaction and TGF-beta signaling induces replication of human pancreatic beta cells. · Pahlavanneshan S, Behmanesh M, Oropeza D, Furuyama K, Tahamtani Y, Basiri M, Herrera PL, Baharvand H · Eur J Cell Biol 2020
    PMID 32646642DOI
    What this evidence cannot show

    Ex vivo human islets, tool compound MI-2, transcript only with no chromatin readout; abstract read, full text not opened. Already cited twice in this corpus. This item exists in this absence entry specifically to stop the absence being stated one claim too wide.

    Evidence that argues against this (1)
    • The beta-cell result narrows the absence but also argues the absence may not matter: if the endocrine CDK-inhibitor response to menin inhibition generalises across endocrine tissues, parathyroid can be predicted rather than measured. Against that, the only other pharmacological measurement of the same axis goes the opposite way in a different tissue, which is precisely why extrapolation is unsafe. Tian S et al. 2025
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    A GEO query for a menin-inhibitor dataset in parathyroid, pituitary or islet returns one series, GSE26978, which is expression profiling of pancreatic islets from Men1fl/fl RIP-Cre mice and their controls - a genetic deletion rather than a drug exposure; a menin AND parathyroid query returns GSE64412 and GSE29674, both also genetic.

    NCBI GEO DataSets esearch and esummary, db=gds, executed 2026-09-23 · Q127 beat, oncofusion knowledge graph · GEO 2026
    What this evidence cannot show

    GEO free-text search over series titles and summaries; a drug-exposed parathyroid dataset deposited without any of these words in its summary would be missed. SRA, ArrayExpress and ProteomeXchange were not searched.

    Evidence that argues against this (1)
    • The archive is not empty of the biology, only of the drug. GSE26978 profiles islets after GENETIC Men1 deletion and its own GEO summary states that the menin complex promotes H3K4me3 at homeobox genes AND cyclin-dependent kinase inhibitor genes. An analyst could argue the genetic series answers the mechanistic question and only the pharmacological confirmation is missing - which would downgrade this absence from never-measured to a narrower pharmacological gap. GEO series depositors 2011
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