DGKα&ζ-IN-2
DGKα/ζ-IN-2 is a potent, orally active and selective dual DGKα/ζ inhibitor with IC50 values of 23 nM (DGKα) and 1.2 nM (DGKζ). DGKα/ζ-IN-2 exhibits selectivity over other DGK isoforms, such as DGKβ and DGKγ. DGKα/ζ-IN-2 shows robust and dose-dependent immune activation in the presence of antigen presentation in an OT-1 murine model. DGKα/ζ-IN-2 can be used for antitumor immunity.
For research use only. We do not sell to patients.
- CAS No.: 3039488-61-1
- Formula: C35H34F4N6O2
- Molecular Weight:646.68
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
DGKα/ζ-IN-2 (compound 17) demonstrates an excellent selectivity across a broad panel of kinases (HPK1, EPHA2, FLT3, KDR, KIT, PDGFRβ and TRKA), with IC50 values > 10 μM[1].
DGKα/ζ-IN-2 demonstrates potent functional activity by promoting IL-2 production in both Jurkat cells (EC50 = 64 nM) and human whole blood (EC50 = 447 nM)[1].
DGKα/ζ-IN-2 exhibits a balanced in vitro ADME profile, with low human microsomal clearance (0.6 L/h/kg), high Caco-2 permeability (1.2 × 10⁻⁶ cm/s), and high solubility in both fasted-state simulated intestinal fluid (> 1000 μg/mL) and simulated gastric fluid (659 μg/mL)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Female OT-I mice[1]
-
Dosage:5, 25, and 50 mg/kg
-
Administration:p.o., single dose
-
Result:Resulted in a dose-dependent increase in CD69+ CD8+ T cells when combined with low dose (0.225 μg) SIINFEKL (HY-P5411), with the highest activation observed at 50 mg/kg.
Partial coverage of the whole blood EC₅₀ was sufficient to achieve full T cell activation.
Did not elicit significant T cell activation alone.
Showed no unexpected deaths or significant adverse effects.
Chemical Information
-
CAS No. 3039488-61-1
-
Molecular Weight 646.68
-
Formula C35H34F4N6O2
-
SMILES
F/C(C1=NC(C2=CC=NN=C2)=CN=C1)=C\C3=CC=C(C(C(F)(F)F)=C3N4CCOC5(C4)CCN(CC5)CC6CC6)OC7=CC=CC=C7
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
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.
-
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)