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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 | |
|---|---|
| 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 | |
|---|---|
| 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 |
| Related IDO Products |
|---|
| IDO-IN-2 (NLG-919 Analogue)
NLG919 is a potent IDO (indoleamine-(2,3)-dioxygenase) pathway inhibitor with Ki/EC50 of 7 nM/75 nM. |
| IDO5L
IDO5L is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC50 of 67 nM. |
| Coptisine
Coptisine, an alkaloid isolated from Coptis, is an effective non-competitive IDO inhibitor with Ki value of 5.8 μM and IC50 value of 6.3 μM. |
| Coptisine chloride
Coptisine chloride is an effective and non-competitive IDO inhibitor with Ki value of 5.8 μM and IC50 value of 6.3 μM. Coptisine chloride is an effective H1N1 neuraminidase (NA-1) inhibitor with IC50 of 104.6 μg/mL, which can be used for influenza A virus (H1N1) infection. |
| Coptisine-Sulfate
Coptisine Sulfate is an alkaloid isolated from coptis coptidis. It is an effective non-competitive IDO inhibitor with Ki value of 5.8 μM and IC50 value of 6.3 μM. |
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