INCB191358
INCB191358 is a selective and orally active inhibitor of diacylglycerol kinase α/ζ/ι (DGKα/ζ/ι ) with IC50 values of 0.12, 0.36 and 0.36 nM. INCB191358 induces antigen-dependent T-cell activation, induces IL-2 production and enhances antitumor efficacy in combination with PD-1 blockade. INCB191358 can be used for the research of cancer, such as colon carcinoma.
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- No. CAS: 3111036-70-2
- Fòrmula: C25H30F3N5O3
- Peso molecular:505.53
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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DGKα 0.12 nM (IC50) |
DGKζ 0.36 nM (IC50) |
DGKι 0.36 nM (IC50) |
DGKβ 8.8 nM (IC50) |
DGKγ 21 nM (IC50) |
IL-2 |
INCB191358 (Compound 52) potently inhibits DGKα (IC50 = 0.12 nM) and DGKζ/ι (IC50 = 0.36 nM) in purified enzyme assays, with high selectivity over off-target Type I DGK isoforms DGKβ and DGKγ[1].
INCB191358 induces IL-2 production in Jurkat T cells with an EC50 of 11 nM[1].
INCB191358 induces IL-2 production in human whole blood with an EC50 of 22 nM[1].
INCB191358 demonstrates balanced in vitro ADME properties, including moderate intrinsic clearance and high Caco-2 permeability[1].
INCB191358 shows no significant cytotoxicity in HEK293 cells, with an IC50 >27 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
INCB191358 (0.3-3 mg/kg; p.o.) enhances antitumor efficacy in combination with anti-PD-1 blockade in MC38 tumor-bearing mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:OT-I transgenic mice (female)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg
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Administration:p.o.; companied with SINFEKL (0.025 μg)
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Result:Induced a dose-dependent increase in CD69+ CD8+ T cells, with the greatest activation observed at 1 mg/kg.
Exceeded the whole blood EC50 (22 nM) at 4 h but fell below the EC50 by 24 h at 1 mg/kg dose.
Resulted in plasma concentrations below the whole blood EC50 at both 4 h and 24 h time points and only modest at 0.1 and 0.3 mg/kg doses.
Did not induce significant T-cell activation when administered as a single agent at 1 mg/kg.
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Animal Model:C57BL/6 mice (female; MC38 syngeneic tumor implanted, treatment initiated day 7 post-implantation)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; in combination with anti-PD-1
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Result:Produced tumor growth inhibition (TGI) of 47% when administered in combination with anti-PD-1 antibody at 0.3 mg/kg.
Achieved significantly greater inhibition with TGI of 78% and 81% when administered in combination with anti-PD-1 antibody at 1 mg/kg and 3 mg/kg doses, respectively.
Showed synergistic activity via Bliss independence analysis for the 1 mg/kg (+19% excess-over-Bliss) and 3 mg/kg (+8.6% excess-over-Bliss) combination groups.
Exhibited minimal antitumor activity with TGI = 19% as a single agent at 1 mg/kg.
Achieved TGI of 48% as a single agent at 3 mg/kg.
Chemical Information
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No. CAS 3111036-70-2
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Peso molecular 505.53
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Fòrmula C25H30F3N5O3
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SMILES
CC1=NC2=C(N1C[C@@H]3CCCO3)N(C(N=C2N4CC[C@@H](C[C@@H]4C)OC5=CC=C(C=C5)C(F)(F)F)=O)C
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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)
INCB191358 Related Classifications
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