In vitro: In IFN-γ–treated human HeLa cells, INCB024360 potently inhibits kynurenine production. INCB024360 also promotes T and natural killer (NK)-cell growth, increases IFN-gamma production, and reduces conversion to regulatory T (T(reg))-like cells.
In vivo: INCB024360 (100 mg/kg, p.o.), via IDO1 inhibition, suppresses kyn generation and tumor growth in immunocompetent, but not immunodeficient, mice. In mice bearing CT26 colon carcinoma, INCB024360 (100 mg/kg, p.o.) also inhibits the growth of IDO-expressing tumors by reducing kynurenine.
Cell Experiment | |
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Cell lines | CEA-specific T-cell |
Preparation method | The IDO1 selective inhibitor epacadostat, obtained through a Cooperative Research and Development Agreement with Incyte Corporation (Wilmington, DE), was dissolved in DMSO and used at different concentrations as described. The concentration used in most experiments, 1.0 μM, was chosen to mimic the serum concentration observed in patients receiving 300 mg BID, where there was > 90% inhibition of IDO1. |
Concentrations | 0, 0.25 or 1.0 μM |
Incubation time | 48 h |
Animal Experiment | |
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Animal models | Female C57BL/6 or Balb/c nu/nu mice bearing PAN02 pancreatic tumors |
Formulation | 3% N,N–Dimethylacetamide, 10% (2-Hydroxypropyl) β-Cyclodextrin Dosages: ~100 mg/kg, twice a day |
Dosages | ~100 mg/kg, twice a day |
Administration | p.o. |
Molecular Weight | 438.23 |
Formula | C11H13BrFN7O4S |
CAS Number | 1204669-58-8 |
Solubility (25°C) | DMSO ≥ 60 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related IDO Products |
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IDO-IN-18
IDO-IN-18 is an IDO inhibitor. |
IDO1-IN-21
IDO1-IN-21 is an IDO1 inhibitor (IC50 = 0.64 μM). |
IDO1-IN-22
IDO1-IN-22 is a IDO1 inhibitor (biochemical hIDO1 IC50: 67.4 nM, HeLa hIDO1 IC50: 17.6 nM). |
IDO1/TDO-IN-6
IDO1/TDO-IN-6 is a dual inhibitor of IDO1/TDO with IC50s of 2.25 and 2.89 μM, respectively. |
IDO-IN-13
IDO-IN-13 is a potent indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with an EC50 of 17 nM, extracted from patent WO2019040102A1, example 43. |
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