Component

ML349, experimental APT2 inhibitor

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. ML349 increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment.

    ML349, experimental APT2 inhibitor → STAT3 palmitoylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    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.
    Complete structured claim and evidence

  2. Treatment with ML349 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T.

    ML349, experimental APT2 inhibitor → Endogenous MAVS S-acylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls
    exposure
    Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C.
    limitations
    Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    organism
    Human
    primary_locator
    SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7.
    primary_references
    https://doi.org/10.1073/pnas.2403392121

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 6–12

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls · source_derived_draft · unverified_draft

    Treatment with ML349 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7. organism: Human experimental_model: Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls exposure: Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C. limitations: Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    Complete structured claim and evidence

  3. ML349 increased the reported IRF3 phosphorylation response despite MAVS knockout in stimulated RAW 264.7 cells.

    ML349, experimental APT2 inhibitor → IRF3 phosphorylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse RAW 264.7; Mavs knockout
    exposure
    ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours.
    limitations
    MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    organism
    Mouse
    primary_locator
    Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 51–57

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse RAW 264.7; Mavs knockout · source_derived_draft · unverified_draft

    ML349 increased the reported IRF3 phosphorylation response despite MAVS knockout in stimulated RAW 264.7 cells. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement. organism: Mouse experimental_model: Mouse RAW 264.7; Mavs knockout exposure: ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours. limitations: MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    Complete structured claim and evidence

  4. ML349 failed to restore the reported IRF3 phosphorylation response in TBK1-knockout RAW 264.7 cells.

    ML349, experimental APT2 inhibitor → IRF3 phosphorylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse RAW 264.7; Tbk1 knockout
    exposure
    ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours.
    limitations
    MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    organism
    Mouse
    primary_locator
    Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 60–66

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse RAW 264.7; Tbk1 knockout · source_derived_draft · unverified_draft

    ML349 failed to restore the reported IRF3 phosphorylation response in TBK1-knockout RAW 264.7 cells. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement. organism: Mouse experimental_model: Mouse RAW 264.7; Tbk1 knockout exposure: ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours. limitations: MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    Complete structured claim and evidence

  5. ML349 increased TBK1 palmitoylation in mouse peritoneal macrophages.

    ML349, experimental APT2 inhibitor → TBK1 palmitoylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Mouse peritoneal exudate macrophages
    exposure
    ML349 concentration series for 12 hours; individual concentrations not transcribed from figure.
    limitations
    Concentration-response result; ABE is an S-acylation assay. No GPX4 endpoint in this experiment.
    organism
    Mouse
    primary_locator
    Figure 3b; ABE and immunoblot.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 69–75

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse peritoneal exudate macrophages · source_derived_draft · unverified_draft

    ML349 increased TBK1 palmitoylation in mouse peritoneal macrophages. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 3b; ABE and immunoblot. organism: Mouse experimental_model: Mouse peritoneal exudate macrophages exposure: ML349 concentration series for 12 hours; individual concentrations not transcribed from figure. limitations: Concentration-response result; ABE is an S-acylation assay. No GPX4 endpoint in this experiment.
    Complete structured claim and evidence

In the sources

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