STAT3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human H358/A549 genetic perturbation experiments.

limitations

This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Changing a signaling protein altered the iron-dependent response.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 276–282

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human H358/A549 genetic perturbation experiments. · source_derived_draft · unverified_draft

## cucurbitacin-b-stat3-rescue Changing a signaling protein altered the iron-dependent response. STAT3 overexpression reversed tested cucurbitacin B-associated lipid ROS and iron changes, whereas STAT3 silencing enhanced them. Model: Human H358/A549 genetic perturbation experiments. Limitations: This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

RNA interference in human breast-cancer cells.

limitations

Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Removing the familiar signaling pathway did not explain this movement effect.

primary_references

Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 172–178

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · RNA interference in human breast-cancer cells. · source_derived_draft · unverified_draft

## cucurbitacin-i-jak-stat-knockdown Removing the familiar signaling pathway did not explain this movement effect. Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells. Model: RNA interference in human breast-cancer cells. Limitations: Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293

evidence_access

Primary abstract

experimental_model

Human NSCLC study with docking and CETSA.

limitations

CETSA is not purified binding kinetics or proof that STAT3 is the sole or selective target.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

The paper tested target engagement as well as signaling.

primary_references

Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 268–274

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC study with docking and CETSA. · source_derived_draft · unverified_draft

## cucurbitacin-b-stat3-engagement The paper tested target engagement as well as signaling. Docking and cellular thermal-shift experiments supported STAT3 target engagement by cucurbitacin B, alongside reduced STAT3 phosphorylation. Model: Human NSCLC study with docking and CETSA. Limitations: CETSA is not purified binding kinetics or proof that STAT3 is the sole or selective target. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805

experimental_model

Human antiestrogen-resistant metastatic breast cancer sample BB3RC61

exposure

5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot.

limitations

The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

organism

Human

primary_locator

Figure 4e; Supplementary Methods: Affinity pull-down assays.

primary_references

https://doi.org/10.1038/s41388-020-1335-z

APT2-STAT3 cycling and a competing sulforaphane target route · lines 87–93

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 · source_derived_draft · unverified_draft

The sulforaphane-derived activity-based probe captured STAT3 from BB3RC61 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4e; Supplementary Methods: Affinity pull-down assays. organism: Human experimental_model: Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 exposure: 5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

experimental_model

Human HBCx34 breast cancer patient-derived xenograft tumor cells

exposure

5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot.

limitations

The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

organism

Human

primary_locator

Figure 4c; Supplementary Methods: Affinity pull-down assays.

primary_references

https://doi.org/10.1038/s41388-020-1335-z

APT2-STAT3 cycling and a competing sulforaphane target route · lines 78–84

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HBCx34 breast cancer patient-derived xenograft tumor cells · source_derived_draft · unverified_draft

The sulforaphane-derived activity-based probe captured STAT3 from HBCX34 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4c; Supplementary Methods: Affinity pull-down assays. organism: Human experimental_model: Human HBCx34 breast cancer patient-derived xenograft tumor cells exposure: 5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

cell_type

mHypoE-44 hypothalamic cells

experimental_model

Knockdown and knockout

limitations

Does not demonstrate direct enzymatic action on STAT3.

organism

mouse

Selenium: literature corrections and mechanism additions · lines 786–796

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Knockdown and knockout · secondary_verified · secondary_verified

## selenom-supports-leptin-stat3-response SELENOM helped these cells respond to leptin. SELENOM depletion reduced leptin-evoked STAT3 phosphorylation in hypothalamic-cell experiments. Organism: mouse Cell type: mHypoE-44 hypothalamic cells Experimental model: Knockdown and knockout Limitations: Does not demonstrate direct enzymatic action on STAT3. Primary reference: [Selenoprotein M Promotes Hypothalamic Leptin Signaling and Thioredoxin Antioxidant Activity](https://pmc.ncbi.nlm.nih.gov/articles/PMC8617589/)

experimental_model

Human HEK293T with expressed APT2 and Flag-STAT3

exposure

Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.

limitations

C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

organism

Human

primary_locator

Figure 2d; Extended Data 7b-c.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

APT2-STAT3 cycling and a competing sulforaphane target route · lines 51–57

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft

APT2-C2S expression did not reproduce the wild-type reduction in STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human HEK293T subcellular fractionation

exposure

LYPLA2 siRNA; exact dose/duration for this panel unresolved.

limitations

Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

organism

Human

primary_locator

Figure 2g; APT2 depalmitoylates p-STAT3.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2-STAT3 cycling and a competing sulforaphane target route · lines 24–30

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T subcellular fractionation · source_derived_draft · unverified_draft

APT2 knockdown reduced nuclear p-STAT3 in the HEK293T fractionation experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2g; APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T subcellular fractionation exposure: LYPLA2 siRNA; exact dose/duration for this panel unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human HEK293T

exposure

LYPLA2 siRNA; exact exposure unresolved.

limitations

Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

organism

Human

primary_locator

Extended Data 7e-f and Results: APT2 depalmitoylates p-STAT3.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2-STAT3 cycling and a competing sulforaphane target route · lines 33–39

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T · source_derived_draft · unverified_draft

APT2 knockdown reduced STAT3 transcriptional activity in the reported HEK293T experiments. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Extended Data 7e-f and Results: APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T exposure: LYPLA2 siRNA; exact exposure unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure.

exposure

LYPLA2 siRNA before Alk14 labeling; Figure 2f states 36 hours before labeling; exact siRNA amount unresolved.

limitations

Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

organism

Human

primary_locator

Figure 2f; Extended Data 7d.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2-STAT3 cycling and a competing sulforaphane target route · lines 15–21

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. · source_derived_draft · unverified_draft

LYPLA2 siRNA increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2f; Extended Data 7d. organism: Human experimental_model: Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. exposure: LYPLA2 siRNA before Alk14 labeling; Figure 2f states 36 hours before labeling; exact siRNA amount unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

experimental_model

Human HEK293T with expressed APT2 and Flag-STAT3

exposure

Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.

limitations

C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

organism

Human

primary_locator

Figure 2d; Extended Data 7b-c.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

APT2-STAT3 cycling and a competing sulforaphane target route · lines 60–66

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft

APT2-S122A expression did not reproduce the wild-type reduction in STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

experimental_model

Human HEK293T with expressed APT2 and Flag-STAT3

exposure

Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.

limitations

C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

organism

Human

primary_locator

Figure 2d; Extended Data 7b-c.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

APT2-STAT3 cycling and a competing sulforaphane target route · lines 42–48

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft

Wild-type APT2 expression reduced STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.

experimental_model

Human HEK293T expressing human DHHC proteins

exposure

Comparison of Flag-tagged human DHHC3, DHHC7 and DHHC19 with HA-STAT3; Alk14 assay.

limitations

Human-construct confirmation is separate from the mouse-DHHC screening experiments. Selected result/legend reviewed; raw gel intensities not reanalyzed.

organism

Human

primary_locator

Extended Data Figure 2f; Results: STAT3 is palmitoylated by DHHC7.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

APT2-STAT3 cycling and a competing sulforaphane target route · lines 69–75

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T expressing human DHHC proteins · source_derived_draft · unverified_draft

Human ZDHHC7 expression increased STAT3 palmitoylation in the human-construct confirmation experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Extended Data Figure 2f; Results: STAT3 is palmitoylated by DHHC7. organism: Human experimental_model: Human HEK293T expressing human DHHC proteins exposure: Comparison of Flag-tagged human DHHC3, DHHC7 and DHHC19 with HA-STAT3; Alk14 assay. limitations: Human-construct confirmation is separate from the mouse-DHHC screening experiments. Selected result/legend reviewed; raw gel intensities not reanalyzed.

experimental_model

Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure.

exposure

20 micromolar ML349 for 36 hours before Alk14 labeling; labeling methods specify 50 micromolar Alk14 for 5 hours.

limitations

Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

organism

Human

primary_locator

Figure 2f; Extended Data 7d; APT2 depalmitoylates p-STAT3.

primary_references

https://doi.org/10.1038/s41586-020-2799-2

APT2-STAT3 cycling and a competing sulforaphane target route · lines 6–12

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. · source_derived_draft · unverified_draft

ML349 increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2f; Extended Data 7d; APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. exposure: 20 micromolar ML349 for 36 hours before Alk14 labeling; labeling methods specify 50 micromolar Alk14 for 5 hours. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.

experimental_model

Human antiestrogen-resistant metastatic breast cancer sample BB3RC61

exposure

72-hour treatment. Supplementary reagent protocol uses 5 micromolar SFX-01, 1 micromolar 4-OH-tamoxifen or 0.1 micromolar fulvestrant; these concentrations are explicitly stated for cell lines, and patient-specific dosing is not independently confirmed here.

limitations

The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

organism

Human

primary_locator

Figure 4d; Results: SFX-01 targets STAT3 signaling.

primary_references

https://doi.org/10.1038/s41388-020-1335-z

APT2-STAT3 cycling and a competing sulforaphane target route · lines 96–102

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 · source_derived_draft · unverified_draft

SFX-01 reduced phosphorylated STAT3 relative to antiestrogen-only treatments in BB3RC61 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4d; Results: SFX-01 targets STAT3 signaling. organism: Human experimental_model: Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 exposure: 72-hour treatment. Supplementary reagent protocol uses 5 micromolar SFX-01, 1 micromolar 4-OH-tamoxifen or 0.1 micromolar fulvestrant; these concentrations are explicitly stated for cell lines, and patient-specific dosing is not independently confirmed here. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.

experimental_model

Human metastatic breast cancer patient-derived sample BB7121

exposure

Prior clinical SFX-01 exposure with progression; ex vivo STAT3 assay. Exact panel exposure unresolved.

limitations

The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli. A single resistant sample does not determine the mechanism of resistance. Supplementary legend/main-text result reviewed; raw image not quantitatively reanalyzed.

organism

Human

primary_locator

Results: SFX-01 targets STAT3 signaling; Supplementary Figure S4c.

primary_references

https://doi.org/10.1038/s41388-020-1335-z

APT2-STAT3 cycling and a competing sulforaphane target route · lines 105–111

Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human metastatic breast cancer patient-derived sample BB7121 · source_derived_draft · unverified_draft

SFX-01 did not repress STAT3 activity in the reported previously SFX-01-treated, resistant BB7121 sample. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Results: SFX-01 targets STAT3 signaling; Supplementary Figure S4c. organism: Human experimental_model: Human metastatic breast cancer patient-derived sample BB7121 exposure: Prior clinical SFX-01 exposure with progression; ex vivo STAT3 assay. Exact panel exposure unresolved. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli. A single resistant sample does not determine the mechanism of resistance. Supplementary legend/main-text result reviewed; raw image not quantitatively reanalyzed.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 6E; Supplementary Figure S5A; Results 3.6.

primary_references

https://doi.org/10.1002/ptr.70245

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 159–165

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine did not increase STAT3 palmitoylation in the reported APT2-D13A/L11A mutant setting. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 6E; Supplementary Figure S5A; Results 3.6. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

25 micromolar solasonine; main methods specify 48-hour cellular drug exposure.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 5D-E; Results 3.5.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 114–120

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine reduced APT2-STAT3 co-immunoprecipitation. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5D-E; Results 3.5. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: 25 micromolar solasonine; main methods specify 48-hour cellular drug exposure. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 123–129

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine suppressed STAT3-driven GPX4 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 132–138

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine suppressed STAT3-driven SLC7A11 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 4B-D; Results 3.4.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 78–84

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine reduced nuclear phosphorylated STAT3, with cytoplasmic accumulation. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 4B-D; Results 3.4. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 5A; Supplementary Figure S4A; Results 3.5.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 69–75

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine increased STAT3 acyl-biotin-exchange signal. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5A; Supplementary Figure S4A; Results 3.5. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 4A; Results 3.4.

primary_references

https://doi.org/10.1002/ptr.70245

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 87–93

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

Solasonine did not change whole-cell phosphorylated STAT3 in the reported immunoblots. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 4A; Results 3.4. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 3A-D and Supplementary Figure S3A-B; Results 3.3.

primary_references

https://doi.org/10.1002/ptr.70245

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 141–147

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

STAT3 siRNA reduced GPX4 mRNA in the reported gallbladder cancer-cell experiments. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3A-D and Supplementary Figure S3A-B; Results 3.3. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human NOZ and GBC-SD gallbladder cancer cells

exposure

siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here.

limitations

Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.

organism

Human

primary_locator

Figure 3A-D and Supplementary Figure S3A-B; Results 3.3.

primary_references

https://doi.org/10.1002/ptr.70245

trigger_kind

machinery_impairment Imported condition classification; unverified.

APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 150–156

Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft

STAT3 siRNA reduced SLC7A11 mRNA in the reported gallbladder cancer-cell experiments. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3A-D and Supplementary Figure S3A-B; Results 3.3. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.