iDeg-6
iDeg-6 is a molecular glue degrader that selectively targets IDO1, with a DC50 of 6.5 nM, an IC50 of 16 nM, and a Kd of 1.46 μM. iDeg-6 competes to bind the heme-binding site of apoprotein IDO1, promoting CRL2KLHDC3-mediated polyubiquitination of IDO1 and neddylation-modification-dependent proteasomal degradation. iDeg-6 reduces kynurenine production, abrogates the non-enzymatic pro-tumor migration function of IDO1, and inhibits tumor growth in immunodeficient mice. iDeg-6 can be used in studies of cancer, infection, and neurological diseases (such as melanoma).
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- Fòrmula: C32H40N2O4S
- Peso molecular:548.74
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
iDeg-6 is a molecular glue degrader that selectively targets IDO1, with a DC50 of 6.5 nM, an IC50 of 16 nM, and a Kd of 1.46 μM. iDeg-6 competes to bind the heme-binding site of apoprotein IDO1, promoting CRL2KLHDC3-mediated polyubiquitination of IDO1 and neddylation-modification-dependent proteasomal degradation. iDeg-6 reduces kynurenine production, abrogates the non-enzymatic pro-tumor migration function of IDO1, and inhibits tumor growth in immunodeficient mice. iDeg-6 can be used in studies of cancer, infection, and neurological diseases (such as melanoma)[1][2][3][4].
IC50 & Target
[1]|
IDO1 6.5 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BXPC-3 | DC50 |
6.5 nM
|
Half-maximal IDO1 protein degradation in IFN-γ-pretreated, washout BxPC3 cells after 24 h incubation measured via immunoblotting.
Half-maximal IDO1 protein degradation in IFN-γ-pretreated, washout BxPC3 cells after 24 h incubation measured via immunoblotting.
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PMC11257573 |
| BXPC-3 | IC50 |
16 nM
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Inhibition of kynurenine formation via indoleamine-2,3-dioxygenase 1 enzymatic activity in IFN-γ-stimulated BxPC3 cells incubated for 48 h, measured by Kyn assay utilizing p-DMAB.
Inhibition of kynurenine formation via indoleamine-2,3-dioxygenase 1 enzymatic activity in IFN-γ-stimulated BxPC3 cells incubated for 48 h, measured by Kyn assay utilizing p-DMAB.
|
41501556 |
| BXPC-3 | IC50 |
14 nM
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Inhibition of kynurenine production in human BxPC3 cells incubated for 48 h with interferon gamma, L-tryptophan, and iDeg-6 measured via cell-based kynurenine pathway inhibition assay.
Inhibition of kynurenine production in human BxPC3 cells incubated for 48 h with interferon gamma, L-tryptophan, and iDeg-6 measured via cell-based kynurenine pathway inhibition assay.
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41310997 |
In Vitro
OthersAnti-cancerMitochondrial FunctionImmune Tolerance & Immunosuppression
Others
iDeg-6 potently inhibits kynurenine formation in IFN-γ-stimulated BxPC3 cells with an IC50 of 16 nM[1].
iDeg-6 (0.5-10000 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated, washout BxPC3 cells with a DC50 of 6.5 nM and a Dmax of 70% at 100 nM[1].
iDeg-6 (0.01-10 µM; 24 h) dose-dependently depletes IDO1 protein in SKOV-3 cells over 24 h of incubation[1].
iDeg-6 (0.01-1 µM; 24 h) dose-dependently depletes IDO1 protein in BT549 cells over 24 h of incubation[1].
iDeg-6 (1-100 nM; 24 h) mediated IDO1 protein depletion in IFN-γ-pretreated, washout wildtype U2OS cells is dependent on KLHDC3, as knockout of KLHDC3 abolishes the degradation and elevates baseline IDO1 levels[1].
iDeg-6 (10-3-105 nM) mediated IDO1 depletion in KBM7-BFP-IDO1 cells is dependent on KLHDC3, as knockout of KLHDC3 abolishes the degradation and elevates baseline IDO1 levels[1].
iDeg-6 (10-10000 nM)-bound full-length IDO1 binds to CRL2KLHDC3 with similar high affinity as apo-IDO1, with an IC50 of 118 nM in a competitive ubiquitination assay[1].
iDeg-6 potently inhibits recombinant human IDO1 enzymatic activity in vitro with an IC50 of 1.6 µM[1].
iDeg-6 (48 h) potently inhibits IDO1 enzymatic activity in IFN-γ-stimulated BxPC3 cells with an IC50 of 16 nM[2].
iDeg-6 (0.5-10000 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated BxPC3 cells with a DC50 of 6.5 nM and a Dmax of 70% at 100 nM[2].
iDeg-6 (0.01-1 μM; 24 h) dose-dependently depletes IDO1 protein in BT549 cells after 24 h of treatment[2].
iDeg-6 (1-100 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated wild-type U2OS cells after 24 h of treatment, and this degradation is dependent on the E3 ligase KLHDC3[2].
iDeg-6 (90 min) potently inhibits in vitro IDO1 enzymatic activity with an IC50 of 1.6 μM[2].
iDeg-6 (50 μM; 3 h) stabilizes recombinant human IDO1 protein in vitro, as measured by nanoDSF, more effectively than iDeg-1, iDeg-2, and iDeg-3[2].
iDeg-6 (100 μM; 3 h) displaces haem from recombinant human holo-IDO1 in vitro, as measured by UV-vis spectroscopy, more effectively than iDeg-1, iDeg-2, and iDeg-3[2].
iDeg-6 (14 nM; 48 h) inhibits kynurenine production in BxPC3 cells with an IC50 of 14 nM[3].
iDeg-6 (14 μM; 45 min) shows weak inhibition of recombinant human IDO1 enzymatic activity, with 40% inhibition at 14 μM and an IC50 >14 μM[3].
iDeg-6 (6.5-100 nM; 24 h) potently degrades IDO1 protein in IFN-γ-stimulated cells with a DC50 of 6.5 nM and 74% maximum degradation at 100 nM[3].
iDeg-6 (25 μM) binds to recombinant human IDO1 with a Kd of 1.46 μM in an enthalpy-driven interaction[3].
iDeg-6 (0.5-10000 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated, washout BxPC3 cells with a DC50 of 6.5 nM and a Dmax of 70% at 100 nM[1].
iDeg-6 (0.01-10 µM; 24 h) dose-dependently depletes IDO1 protein in SKOV-3 cells over 24 h of incubation[1].
iDeg-6 (0.01-1 µM; 24 h) dose-dependently depletes IDO1 protein in BT549 cells over 24 h of incubation[1].
iDeg-6 (1-100 nM; 24 h) mediated IDO1 protein depletion in IFN-γ-pretreated, washout wildtype U2OS cells is dependent on KLHDC3, as knockout of KLHDC3 abolishes the degradation and elevates baseline IDO1 levels[1].
iDeg-6 (10-3-105 nM) mediated IDO1 depletion in KBM7-BFP-IDO1 cells is dependent on KLHDC3, as knockout of KLHDC3 abolishes the degradation and elevates baseline IDO1 levels[1].
iDeg-6 (10-10000 nM)-bound full-length IDO1 binds to CRL2KLHDC3 with similar high affinity as apo-IDO1, with an IC50 of 118 nM in a competitive ubiquitination assay[1].
iDeg-6 potently inhibits recombinant human IDO1 enzymatic activity in vitro with an IC50 of 1.6 µM[1].
iDeg-6 (48 h) potently inhibits IDO1 enzymatic activity in IFN-γ-stimulated BxPC3 cells with an IC50 of 16 nM[2].
iDeg-6 (0.5-10000 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated BxPC3 cells with a DC50 of 6.5 nM and a Dmax of 70% at 100 nM[2].
iDeg-6 (0.01-1 μM; 24 h) dose-dependently depletes IDO1 protein in BT549 cells after 24 h of treatment[2].
iDeg-6 (1-100 nM; 24 h) dose-dependently depletes IDO1 protein in IFN-γ-pretreated wild-type U2OS cells after 24 h of treatment, and this degradation is dependent on the E3 ligase KLHDC3[2].
iDeg-6 (90 min) potently inhibits in vitro IDO1 enzymatic activity with an IC50 of 1.6 μM[2].
iDeg-6 (50 μM; 3 h) stabilizes recombinant human IDO1 protein in vitro, as measured by nanoDSF, more effectively than iDeg-1, iDeg-2, and iDeg-3[2].
iDeg-6 (100 μM; 3 h) displaces haem from recombinant human holo-IDO1 in vitro, as measured by UV-vis spectroscopy, more effectively than iDeg-1, iDeg-2, and iDeg-3[2].
iDeg-6 (14 nM; 48 h) inhibits kynurenine production in BxPC3 cells with an IC50 of 14 nM[3].
iDeg-6 (14 μM; 45 min) shows weak inhibition of recombinant human IDO1 enzymatic activity, with 40% inhibition at 14 μM and an IC50 >14 μM[3].
iDeg-6 (6.5-100 nM; 24 h) potently degrades IDO1 protein in IFN-γ-stimulated cells with a DC50 of 6.5 nM and 74% maximum degradation at 100 nM[3].
iDeg-6 (25 μM) binds to recombinant human IDO1 with a Kd of 1.46 μM in an enthalpy-driven interaction[3].
Anti-cancer
Mitochondrial Function
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
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Cell Line:IFN-γ-pretreated, washout BxPC3 cells
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Concentration:0.5-10000 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels, with a Dₘₐₓ of 70% at 100 nM and a DC50 of 6.5 nM.
Western Blot Analysis[1]
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Cell Line:SKOV-3 cells
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Concentration:0.01-10 µM
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Incubation Time:24 h
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Result:Reduced IDO1 protein levels in a dose-dependent manner.
Western Blot Analysis[1]
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Cell Line:BT549 cells
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Concentration:0.01-1 µM
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Incubation Time:24 h
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Result:Reduced IDO1 protein levels in a dose-dependent manner.
Western Blot Analysis[1]
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Cell Line:wildtype and KLHDC3 knockout U2OS cells (IFN-γ-pretreated with washout)
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Concentration:1-100 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels in wildtype U2OS cells.
Failed to reduce IDO1 protein levels in KLHDC3 knockout U2OS cells, which remained elevated compared to wildtype cells.
Western Blot Analysis[2]
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Cell Line:IFN-γ-pretreated BxPC3 cells
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Concentration:0.5-10000 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels, achieving a maximal achievable degradation (Dₘₐₓ) of 70% at 100 nM, with a half-maximal degradation concentration (DC50) of 6.5 nM.
Western Blot Analysis[2]
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Cell Line:unstimulated and IFN-γ-stimulated SKOV-3 cells
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Concentration:0.01-10 μM (unstimulated SKOV-3); 0.01-1 μM (IFN-γ-stimulated SKOV-3)
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels in both unstimulated and IFN-γ-stimulated SKOV-3 cells.
Western Blot Analysis[2]
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Cell Line:BT549 cells
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Concentration:0.01-1 μM
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels.
Western Blot Analysis[2]
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Cell Line:wild-type and KLHDC3 knockout U2OS cells
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Concentration:1-100 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced IDO1 protein levels in wild-type U2OS cells, but this depletion was rescued in KLHDC3 knockout U2OS cells.
In Vivo
Anti-cancer
iDeg-6 (30 mg/kg; i.p.; twice daily; 18 days) significantly inhibits SKOV-3 tumor growth and prolongs survival in NSG immunodeficient mice without inducing related toxicity[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG immunodeficient[3]
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Dosage:30 mg/kg
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Administration:i.p.; twice daily; 18 days
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Result:Inhibited SKOV-3 tumor growth significantly.
Showed no significant negative impact on body weight, with a slight body weight recovery observed.
Improved overall mouse survival significantly compared to vehicle control.
Chemical Information
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Peso molecular 548.74
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Fòrmula C32H40N2O4S
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SMILES
C#CC1=CC=C(C=C1)NC(OC[C@@]23[C@H](C[C@@H]4C[C@]2([H])CN(C3)S(C5=C(C)C=C(C(C)(C)C)C=C5)(=O)=O)C4(C)C)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Select Batch:
Pureza:
99.98%
Assay:
99.98%
ee.:
99.98%
Referencias
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iDeg-6 Related Classifications
HY-177785 Related Classifications
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