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Epacadostat

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Chemical Structure| 1204669-58-8 同义名 : INCB 024360
CAS号 : 1204669-58-8
货号 : A205097
分子式 : C11H13BrFN7O4S
纯度 : 99%+
分子量 : 438.233
MDL号 : MFCD26142934
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(239.6 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+40% PEG 300+5% TWEEN 80+50 % water 4.35 mg/mL

生物活性
描述 IDO1 (Indoleamine 2,3-dioxygenase-1) is a heme-containing monomeric oxidoreductase, which can catalyze the degradation of the essential amino acid tryptophan to N-formyl-kynurenine, an intermediate metabolized through a series of steps to form NAD+. IDO1 is considered to play an important role in the induction of tumor immune tolerance, which can regulate the immunosuppressive mechanisms responsible for tumor escape from host immune surveillance. Epacadostat is a selective IDO1 inhibitor with IC50 value of ~10nM with little activity against the related enzymes IDO2 or TDO. Treatment with INCB024360 at concentration ranging in 1nM-1000nM for 2 days dose-dependently inhibit the kynurenine production in HeLa cells induced IDO1 production by IFN-γ, but did not affect the protein level of IDO1. Dose-dependent reverse of the suppression on T-cell proliferation by co-culture of HeLaIDO1+/ DCsIDO1+ in the presence of a soluble anti-CD3 antibody and human recombinant IL-2/ IFN-γ, LPS, or PGN can be observed by addition of Epacadostat at concentration ranging in 3-2000nM for 2 days. This reverse can also be observed in CD4+T cells, CD8+T cells, and NK cells treated with Epacadostat in the presence of DCIDO1+ cells. Also addition of Epacadostat at 1μM for 6 days could reduce the conversion of naive CD4+CD25- T cells to regulatory T cells induced by cocultured DCIDO1+ cells, which is associated with tumor growth while regulatory T cells depletion enhances antitumor immune responses. Oral administration of Epacadostat at 25mg/kg or 100mg/kg twice a day can reduced tumor growth by 37% and 57% in female C57BL/6 mice bearing PAN02 pancreatic cancer cells and this was lymphocyte-dependent[1].
作用机制 INCB024360 is a reversible and competitive inhibitor of IDO1, but not a substrate of the IDO1 enzyme.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.28mL

0.46mL

0.23mL

11.41mL

2.28mL

1.14mL

22.82mL

4.56mL

2.28mL
参考文献

[1]Dhiman V, Giri KK, et al. Determination of epacadostat, a novel IDO1 inhibitor in mouse plasma by LC-MS/MS and its application to a pharmacokinetic study in mice. Biomed Chromatogr. 2017 Feb;31(2).

[2]Affolter T, Llewellyn HP, et al. Inhibition of immune checkpoints PD-1, CTLA-4, and IDO1 coordinately induces immune-mediated liver injury in mice. PLoS One. 2019 May 21;14(5):e0217276.

[3]Fu R, Zhang YW, et al. LW106, a novel indoleamine 2,3-dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma-immune crosstalk and cancer stem cell enrichment in tumour micro-environment. Br J Pharmacol. 2018 Jul;175(14):3034-3049.