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.
For research use only. We do not sell to patients.
- Formula: C33H32N2O5Se
- Molecular Weight:615.58
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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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Biological Activity
Description
In Vitro
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. Further protocols information, click here.
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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.
Parmacokinetics
| 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 % |
In Vivo
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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Molecular Weight 615.58
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Formula 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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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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PD-L1-IN-12 Related Classifications
HY-184989 Related Classifications
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