PD-L1-IN-12
PD-L1-IN-12 is an orally active and potent selenium-containing small-molecule PD-L1 inhibitor (KD = 9.06 nM). PD-L1-IN-12 can mediate the internalization of PD-L1 and strongly block hPD-1 and hPD-L1 interaction (IC50 = 5.2 nM). PD-L1-IN-12 can be used in colorectal cancer immunology research.
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- Fòrmula: C33H32N2O5Se
- Peso molecular:615.58
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Actividad biológica
PD-L1-IN-2 (compound SA13) (recombinant Tag1-PD-L1 and Tag2-PD-1 proteins; 3 h) strongly inhibited the PD-1/PD-L1 interaction with IC50 = 5.2 nM[1].
PD-L1-IN-2 (recombinant hPD-L1 Protein (HY-P73361); 15-960 nM) exhibits a strong binding affinity to the hPD-L1 protein with KD = 9.06 nM[1].
PD-L1-IN-2 (1-32 μM; 48 h) exhibits minimal direct cytotoxicity across various tumor cell lines (hPD-L1MC38, MDA-MB-231, RKO, SK-N-SH, NCI-H292, SK-N-AS, MCF-7, HT-29, A549) and normal cells (MRC-5, PBMCs), showing non-specific cytotoxicity only at very high concentrations[1].
PD-L1-IN-2 (100 nM or 7.8-1000 nM; 30 min) effectively blocks the binding between PD-1 and PD-L1 proteins in HEK-293T cells (co-incubated with exogenous PD-L1-Fc protein) with IC50 = 25.26 nM[1].
PD-L1-IN-2 (1 μM or 0.008-8 μM; 16 h) downregulates cell-surface PD-L1 expression in a significant, dose-dependent manner and induces PD-L1 internalization in tumor cells (hPD-L1MC38 (IC50 = 113.6 nM)、MDA-MB-231 (IC50 = 378.5 nM)、RKO (IC50 = 101.0 nM))[1].
PD-L1-IN-2 (0.016-8 μM; 16 h) also significantly induces the downregulation of cell-surface PD-L1 expression in HEK-293T cells overexpressing PD-L1-GFP (IC50 = 517.1 nM), confirming that this downregulation results from internalization rather than epitope competition or steric masking[1].
PD-L1-IN-2 (1-8 μM) does not reduce total PD-L1 protein expression in hPD-L1MC38 cells[1].
PD-L1-IN-2 (1 μM; 8 h) significantly induces the co-localization of internalized PD-L1 with the early endosome marker Rab5 in HEK-293T cells overexpressing PD-L1-GFP[1].
PD-L1-IN-2 (1-8 μM; 48 h) reverses the immunosuppressive effects of PD-L1 in a dose-dependent manner in CD3/CD28 antibody-activated PBMCs (co-incubated with exogenous PD-L1 protein), effectively restoring the ability of suppressed T cells to secrete interferon-gamma (IFN-γ)[1].
PD-L1-IN-2 (1-32 μM; 48 h) induces significant, dose-dependent immune-mediated cytotoxicity against tumor cells with high PD-L1 expression (hPD-L1MC38, MDA-MB-231), while exhibiting no significant cytotoxicity against tumor cell lines with low PD-L1 expression (MCF-7, A549) n a co-culture system of tumor cells and PBMCs (tumor cell:PBMC ratio of 1:10). PD-L1-IN-2 promotes PBMC-mediated immune killing of tumor cells primarily by blocking the PD-1/PD-L1 axis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Tumor cells (hPD-L1MC38, MDA-MB-231, RKO, SK-N-SH, NCI-H292, SK-N-AS, MCF-7, HT-29, A549), normal human fetal lung fibroblast cells MRC-5 and PBMCs
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Concentration:1 μM, 2 μM, 4 μM, 8 μM,16 μM,32 μM
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Incubation Time:48 h
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Result:Exhibited minimal direct toxicity toward both tumor and normal cells at lower concentrations, proving its anti-tumor efficacy was not due to direct cytotoxicity.
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Cell Line:PD-L1-GFP-expressing HEK-293T cells
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Concentration:1 μM
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Incubation Time:
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Result:Induced the transport of cell-surface PD-L1 to early endosomes via Rab5-mediated endocytosis.
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Cell Line:PBMCs (activated with CD3/CD28 antibodies and co-cultured with PD-L1 protein)
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Concentration:1 μM, 2 μM, 4 μM, 8 μM
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Incubation Time:48 h
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Result:Reversed the immunosuppressive effect of PD-L1 in a dose-dependent manner and effectively restored the IFN-γsecretion function of T cells.
| Species | Dose | Route | AUC0-24 | AUC0-∞ | Cmax | CL | T1/2 | Tmax | Vd | F |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 12 mg/kg | i.v. | 41538.52 μg/L·h | 41710.70 μg/L·h | 24646.20 μg/L | 0.29 L/h/kg | 1.92 h | 0.083 h | 0.65 L/kg | / |
| Rat[1] | 20 mg/kg | i.g. | 33990.50 μg/L·h | 36654.22 μg/L·h | 3796.60 μg/L | 0.62 L/h/kg | 5.01 h | 2.8 h | 3.96 L/kg | 52.73 % |
| Rat[1] | 60 mg/kg | i.g. | 100588.55 μg/L·h | 111374.68 μg/L·h | 8340.80 μg/L | 0.56 L/h/kg | 6.42 h | 4.0 h | 5.01 L/kg | 53.4 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6 mice (5-6 weeks old, 16-20 g) were subcutaneously injected with 5 × 105 hPD-L1MC38 cells in the right axilla[1].
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Dosage:20 mg/kg, 40 mg/kg, 60 mg/kg
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Administration:i.g.; once daily; for 14 days
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Result:Exhibited significant tumor growth inhibition. In the 60 mg/kg dose group, the tumor growth inhibition (TGI) rate reached 77.79%.
Significantly increased the proportion of CD3+CD8+ cytotoxic T lymphocytes (CTLs) in tumor-infiltrating tissues, the spleen, and peripheral blood (reaching 54.1%, 30.4%, and 20.6%, respectively) and significantly raised the CD8+/CD4+ T-cell ratio.
Significantly upregulated the mRNA expression levels of the chemokines CXCL9 and CXCL10 in tumor tissues, while PD-L1 mRNA showed a downward trend at a dose of 60 mg/kg.
Significantly enhanced the protein expression of the effector molecules Granzyme B and Perforin in tumor tissues at a dose of 40 mg/kg and 60 mg/kg.
Did not induce significant hepatic or renal toxicity.
Chemical Information
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Peso molecular 615.58
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Fòrmula C33H32N2O5Se
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SMILES
C[Se]C1=CC(C2=CC=CC(COC3=CC(OCC4=CC=CC(C#N)=C4)=C(CN[C@H](C(O)=O)CO)C=C3)=C2C)=CC=C1
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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
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PD-L1-IN-12 Related Classifications
HY-184989 Related Classifications
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