INCB 024360 is a potent and selective IDO1 inhibitor with IC50 of 71.8 nM±17.5 nM.
Description
INCB 024360 is a potent and selective IDO1 inhibitor with IC50 of 71.8 nM±17.5 nM.
IC50 & Target
IC50: 71.8 nM±17.5 nM (IDO1), 7.1 nM±0.6 nM (IDO1, in HeLa cells)[1]
In Vitro
In cellular assays, INCB 024360 (INCB024360) selectively inhibits human IDO1 with IC50 values of approximately 10 nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). INCB 024360 also exhibits significant activity toward mouse IDO1, with an IC50 value of 52.4 nM±15.7 nM, in a similar assay using mouse IDO1-transfected HEK293/MSR cells[1].
In Vivo
Female Balb/c mice bearing CT26 tumors are treated orally twice daily for 12 d with INCB 024360 (INCB024360) at 100 mg/kg. INCB 024360 suppresses kynurenine equivalently in plasma, tumors, and lymph nodes. In naïve C57BL/6 mice, 50 mg/kg INCB024360 decreases plasma kynurenine levels within 1 hour and those levels stay at least 50% suppressed through the 8-hour time course[2].
Clinical Trial
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References
[1]. Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.
[2]. Koblish HK, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.
Preparing Stock Solutions
ConcentrationVolumeMass
1 mg
5 mg
10 mg
1 mM
2.2819 mL
11.4095 mL
22.8191 mL
5 mM
0.4564 mL
2.2819 mL
4.5638 mL
10 mM
0.2282 mL
1.1410 mL
2.2819 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]
INCB 024360 (INCB024360) is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].
To determine INCB 024360 activity against IDO in recombinant cells, HEK293/MSR cells are transiently transfected with full-length human or mouse IDO1, or mouse IDO2 cDNA, with Transit-293 transfection reagent or Lipofectamine 2000 reagents. INCB 024360 at different concentrations is added to the recovered transfected cells seeded at 2×104 cells per well in a 96-well plate (200 μL/well). The cells are incubated for 2 days, and kyn in the supernatants is measured as described in the HeLa cell assay. The tryptophan 2,3-dioxygenase (TDO) assay is performed similarly with HEK293/MSR cells transfected with a human TDO expression vector[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[2]
INCB 024360 (INCB024360) is prepared in 40% N,N-Dimethylacetamide, 60% propylene glycol (Mice)[2].
Mice[2]
The female C57BL/6 mice are dosed orally with 50 mg/kg INCB 024360. C57BL/6 wild-type or Ido1-/--deficient mice are administered a single oral dose of INCB 024360, at which point food is removed from the cages until after the 8-h time point. At various time points after dosing, mice are euthanized and blood is collected by cardiac puncture. Plasma is analyzed for the presence of INCB023843, INCB 024360, tryptophan, and kynurenine according to the methods below. Data are analyzed using one-way ANOVA with Dunnett"s posttest for statistical significance. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
[1]. Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.
[2]. Koblish HK, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.
Molecular Weight
438.23
Formula
C₁₁H₁₃BrFN₇O₄S
CAS No.
1204669-58-8
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Shipping
Room temperature in continental US; may vary elsewhere
[1]. Liu X, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.
[2]. Koblish HK, et al. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.
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