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 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 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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||67 mg/mL in DMSO|
The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells.
Jochems C, et al. Oncotarget. 2016 Jun 21;7(25):37762-37772. PMID: 27192116.
Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor.
Shi JG, et al. J Clin Pharmacol. 2016 Nov;56(11):1344-1354. PMID: 26990117.
|Related IDO Products|
Indoximod, also known as NLG8189 and D-1MT is an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor with a Ki value of 19 μM.
IDO-IN-1 is a potent and selective indoleamine-2,3-dioxygenase (IDO) inhibitor with IC50 of 59 nM.
IDO-IN-2 is an IDO inhibitor extracted from patent WO/2015031295 A1, compound example 1, has IC50 values of 0.068 μM in HeLa cell and 0.16 μM in HEK293 cell.
BMS-986205 is a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor.
INCB024360 is a potent IDO1 inhibitor (IC50 value of 10 nM) with desirable pharmaceutical properties.
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