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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 |
|---|
| (S)-LY-3381916
(S)-LY-3381916 is an active S-isomer of LY-3381916. (S)-LY-3381916 binds to IDOL with an IC50 value less than 1.5 µΜ. LY-3381916 is a potent, selective and brain penetrated inhibitor of Indoleamine 2,3-Dioxygenase 1 (IDO1) activity, binds to apo-IDO1 lacking heme rather than mature heme-bound IDO1. |
| IDO2-IN-1
IDO2-IN-1 is an orally active and potent Indoleamine 2,3-dioxygenase 2 (IDO2) inhibitor with an IC50 value of 112 nM. IDO2-IN-1 can be used for the research of inflammatory autoimmunity. |
| IDO1/2-IN-1
IDO1/2-IN-1 is the first potent IDO1/IDO2 dual inhibitor with IC50s of 28 nM and 144 nM for IDO1 and IDO2, respectively. |
| IDO1/2-IN-1 hydrochloride
IDO1/2-IN-1 hydrochloride is the first potent IDO1/IDO2 dual inhibitor with IC50s of 28 nM and 144 nM for IDO1 and IDO2, respectively. |
| IDO-IN-18
IDO-IN-18 is an IDO inhibitor. |
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