PDL1 degrader-3
PDL1 degrader-3 (compound e24) is a DUBTAC-like PD-L1 degrader. PDL1 degrader-3 inhibits CSN5 enzymatic activity, increases PD-L1 ubiquitination, and induces PD-L1 degradation via the ubiquitin-proteasome pathway, reducing PD-L1 expression on tumor cell membranes. PDL1 degrader-3 blocks PD-1/PD-L1 interaction, activates the tumor immune microenvironment, enhances tumor-infiltrating T-cell immunity, and inhibits activation of immunosuppressive MDSCs and Tregs. PDL1 degrader-3 exerts antitumor effects in mouse tumor models. PDL1 degrader-3 can be used for the research of colorectal cancer, lung cancer.
For research use only. We do not sell to patients.
- CAS No.: 2488699-00-7
- Formula: C16H12N2O2
- Molecular Weight:264.28
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
PDL1 degrader-3 (comppund e24) (20 μM; 24 h) potently reduces PD-L1 protein expression in human colorectal cancer RKO cells, with activity superior to JQ-1 and low cytotoxicity[1].
PDL1 degrader-3 (1-20 μM; 3-24 h) dose- and time-dependently reduces PD-L1 protein expression in human colorectal cancer RKO cells and human lung cancer H1975 cells, with significant downregulation observed at concentrations ≥5 μM (RKO) or ≥10 μM (H1975) after 24 h, and at 20 μM starting at 3 h for both cell lines[1].
PDL1 degrader-3 (5-20 μM; 3-24 h) dose- and time-dependently reduces plasma membrane PD-L1 expression in human colorectal cancer RKO cells and human lung cancer H1975 cells, with significant downregulation observed at 10 and 20 μM after 24 h, and at 20 μM starting at 6 h for both cell lines[1].
PDL1 degrader-3 (5-20 μM; 24 h) dose-dependently reduces PD-L1 protein expression in human colorectal cancer RKO cells and human lung cancer H1975 cells, as measured by immunofluorescence, with significant downregulation at 10 and 20 μM after 24 h[1].
PDL1 degrader-3 (5-20 μM; 24 h) does not significantly reduce cell viability in human colorectal cancer RKO cells or human lung cancer H1975 cells at concentrations up to 20 μM for 24 h[1].
PDL1 degrader-3 (20 μM; 24 h) significantly inhibits PD-L1/PD-1 binding in human colorectal cancer RKO cells and human lung cancer H1975 cells[1].
PDL1 degrader-3 (5-20 μM; 24 h) dose-dependently enhances T cell-mediated killing of human colorectal cancer RKO cells and human lung cancer H1975 cells[1].
PDL1 degrader-3 (1-20 μM; 3-24 h) does not significantly affect PD-L1 mRNA expression in human colorectal cancer RKO cells at concentrations up to 20 μM for up to 24 h, indicating PD-L1 downregulation occurs at the protein level[1].
PDL1 degrader-3 (20 μM; up to 12 h) significantly reduces PD-L1 protein half-life in human colorectal cancer RKO cells when co-treated with 60 μg/mL CHX for up to 12 h[1].
PDL1 degrader-3 (20 μM; 12 h) induces PD-L1 degradation via the ubiquitin-proteasome pathway in human colorectal cancer RKO cells and human lung cancer H1975 cells, as this effect is blocked by 10 μM MG132 but not by lysosomal or autophagy inhibitors[1].
PDL1 degrader-3 (20 μM; 6 h) significantly increases PD-L1 polyubiquitination levels in human colorectal cancer RKO cells, confirming degradation via the ubiquitin-proteasome pathway[1].
PDL1 degrader-3 (20 μM; 24 h post-transfection) induced PD-L1 downregulation in human colorectal cancer RKO cells is dependent on CSN5, as overexpression of CSN5 blocks the effect and knockdown enhances it[1].
PDL1 degrader-3 (10-320 μM; 3 min) directly binds to CSN5 protein in human colorectal cancer RKO cells, as indicated by increased CSN5 thermal stability in a concentration-dependent manner[1].
PDL1 degrader-3 specifically binds to wild-type CSN5 with a Kd of 4.53 μM, with critical binding interactions mediated by Asp151 and Lys210 residues[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human colorectal cancer RKO cells
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Concentration:20 μM
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Incubation Time:24 h
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Result:Reduced PD-L1 protein expression more effectively than the positive control JQ-1.
Showed minimal cytotoxicity at 20 μM.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:1-20 μM (24 h treatment); 20 μM (time-course treatment)
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Incubation Time:24 h (concentration-gradient treatment); 3-24 h (20 μM treatment)
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Result:Caused concentration-dependent reduction in PD-L1 protein levels in RKO cells, with significant decreases at 5, 10, 15, 20 μM after 24 h.
Caused time-dependent reduction in RKO cells, with significant decreases starting at 3 h with 20 μM.
Caused concentration-dependent reduction in H1975 cells, with significant decreases at 10, 15, 20 μM after 24 h.
Caused time-dependent reduction in H1975 cells, with significant decreases starting at 3 h with 20 μM.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:5-20 μM
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Incubation Time:24 h
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Result:Caused concentration-dependent reduction in PD-L1 fluorescence intensity in both RKO and H1975 cells, with significant decreases at 10 and 20 μM.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:5-20 μM
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Incubation Time:24 h
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Result:Did not significantly reduce cell viability in either RKO or H1975 cells, with no significant differences compared to the control group.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:20 μM
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Incubation Time:24 h
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Result:Significantly reduced green fluorescence intensity in both RKO and H1975 cells, indicating a significant decrease in PD-L1/PD-1 binding.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:5-20 μM
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Incubation Time:24 h
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Result:Significantly enhanced T cell-mediated killing of RKO and H1975 cells, with a concentration-dependent reduction in surviving tumor cells.
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Cell Line:human colorectal cancer RKO cells
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Concentration:1-20 μM (24 h treatment); 20 μM (time-course treatment)
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Incubation Time:24 h (concentration-gradient treatment); 3-24 h (20 μM treatment)
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Result:Did not significantly alter PD-L1 mRNA levels compared to the control in RKO cells after 24 h at 1-20 μM.
Did not significantly alter PD-L1 mRNA levels compared to the control in RKO cells at 20 μM for 3-24 h.
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Cell Line:human colorectal cancer RKO cells
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Concentration:20 μM (co-treated with 60 μg/mL CHX)
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Incubation Time:0-12 h
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Result:Significantly reduced the half-life of PD-L1 protein in RKO cells compared to treatment with CHX alone.
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Cell Line:human colorectal cancer RKO cells, human lung cancer H1975 cells
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Concentration:20 μM (co-treated with 1-10 μM MG132; 20-40 μM CQ; 20-40 μM 3-MA)
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Incubation Time:12 h
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Result:Co-treatment with 20 μM and 10 μM MG132 completely blocked the PDL1 degrader-3-induced reduction in PD-L1 protein levels in both RKO and H1975 cells.
Co-treatment with 20 μM and 20, 40 μM CQ or 20, 40 μM 3-MA did not block PD-L1 reduction in both RKO and H1975 cells.
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Cell Line:human colorectal cancer RKO cells
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Concentration:20 μM (co-treated with MG132)
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Incubation Time:6 h
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Result:Significantly increased the polyubiquitination level of PD-L1 protein in RKO cells.
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Cell Line:human colorectal cancer RKO cells
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Concentration:20 μM
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Incubation Time:24 h (post-transfection with CSN5 overexpression plasmid or siRNA for 24 h)
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Result:Overexpression of CSN5 completely reversed the PDL1 degrader-3-induced reduction in PD-L1 protein levels.
Knockdown of CSN5 enhanced the PDL1 degrader-3-induced reduction in PD-L1 protein levels.
PDL1 degrader-3 (2.5-5 mg/kg; i.p.; daily; 16 days) inhibits subcutaneous Lewis lung cancer growth in C57BL/6J mice with an 88.56% tumor growth inhibition rate at 5 mg/kg, while modulating the tumor immune microenvironment to enhance antitumor immunity[1].
PDL1 degrader-3 (10 mg/kg; i.p.; daily; 16 days) does not inhibit subcutaneous MC38 colorectal cancer growth in T-cell-deficient nude mice, confirming its antitumor activity requires functional T cells[1].
PDL1 degrader-3 (5 mg/kg; i.p.; daily; 16 days) does not inhibit subcutaneous Lewis lung cancer growth in T-cell-deficient nude mice, confirming its antitumor activity requires functional T cells[1].
PDL1 degrader-3 (10 mg/kg; i.p.; daily; 18 days) in combination with anti-CTLA-4 antibody enhances antitumor immunity and suppresses subcutaneous MC38 colorectal cancer growth in C57BL/6J mice more effectively than either monotherapy[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (female, 6 weeks old, subcutaneous injection of 8 × 105 MC38 mouse colorectal cancer cells)[1]
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Dosage:2.5 mg/kg; 5 mg/kg; 10 mg/kg
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Administration:i.p.; daily; 16 days
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Result:Achieved a 38.79% tumor growth inhibition rate at 2.5 mg/kg.
Achieved a 53.09% tumor growth inhibition rate at 5 mg/kg.
Achieved a 78.88% tumor growth inhibition rate at 10 mg/kg.
Reduced the frequency of tumor-infiltrating FOXP3+CD25+ Tregs from 34.2% in controls to 25.2%, 17.0%, and 6.81% at 2.5, 5, and 10 mg/kg respectively.
Reduced the frequency of CD11b+Gr-1+ MDSCs from 30.1% in controls to 23.9%, 14.9%, and 10.2% at 2.5, 5, and 10 mg/kg respectively.
Increased the frequency of GzmB+ CD8+ T cells from 4.53% in controls to 10.7%, 15.5%, and 26.3% at 2.5, 5, and 10 mg/kg respectively.
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Animal Model:C57BL/6J (female, 6 weeks old, subcutaneous injection of 8 × 105 Lewis mouse lung cancer cells)[1]
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Dosage:2.5 mg/kg; 5 mg/kg
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Administration:i.p.; daily; 16 days
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Result:Achieved a 9.16% tumor growth inhibition rate at 2.5 mg/kg.
Achieved an 88.56% tumor growth inhibition rate at 5 mg/kg.
Reduced tumor-infiltrating immunosuppressive cells.
Increased activated CD8+ T cell frequency in tumor tissue.
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Animal Model:C57BL/6J (female, 6 weeks old, subcutaneous injection of 8 × 105 MC38 mouse colorectal cancer cells)[1]
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Dosage:10 mg/kg (in combination with anti-CTLA-4 antibody 100 μg per mouse)
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Administration:i.p.; daily (e24), every 5 days (anti-CTLA-4); 18 days
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Result:Resulted in greater tumor growth inhibition than either monotherapy.
Reduced tumor weight significantly compared to controls.
Reduced tumor-infiltrating FOXP3+CD25+ Tregs to 4.24%.
Reduced CD11b+Gr-1+ MDSCs to 9.03%.
Increased GzmB+ CD8+ T cells to 35.3%.
Reduced FOXP3 expression and increased CD3 expression in tumor tissue compared to controls and monotherapy groups.
Chemical Information
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CAS No. 2488699-00-7
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Molecular Weight 264.28
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Formula C16H12N2O2
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SMILES
COC1=C(C=C(C2=C1)C=NC3=C2C(C#N)=CC=C3)OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PDL1 degrader-3 Related Classifications
HY-182239 Related Classifications
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