product name INCB024360 analogue
Description: INCB024360 analogue, also known as IDO-IN-2, is a potent, orally available hydroxyamidine, competitive inhibitor of IDO1 (indoleamine-(2,3)-dioxygenase) with IC50 of 67 nM. INCB024360 analog has potential immunomodulating and antineoplastic activities. In vivo testing of INCB024360 analog in mice demonstrated pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (>50%) in plasma and dose dependent efficacy.
References: J Med Chem. 2009 Dec 10;52(23):7364-7; Blood. 2010 Apr 29;115(17):3520-30.
271.64
Formula
C9H7ClFN5O2
CAS No.
914471-09-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 54 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: 54 mg/mL (198.8 mM)
Solubility (In vivo)
2% DMSO+corn oil: 5mg/mL
Synonyms
IDO-IN-2
other peoduct :
| In Vitro |
In vitro activity: In HeLa cells, INCB024360 shows higher inhibitory activity on IDO1 with IC50 of 19 NM. In coculture systems of human allogeneic lymphocytes with dendritic cells or tumor cells, INCB024360, via IDO1 inhibition, reverses T-cell suppression mediated by IDO-expressing HeLa cells or DCs, and increases the proliferation and functional activity of CD4+ T cells, CD8+ T cells, and NK cells. Kinase Assay: Human IDO with an N-terminal His tag was expressed in E.coli and purified to homogeneity. IDO catalyzed the oxidative cleavage of the pyrrole ring of the indole nucleus of tryptophan to yield N’-formylkynurenine. The assays were performed at room temperature using 20 nM IDO and 2 mM D-Trp in the presence of 20 mM ascorbate, 3.5 μM methylene blue and 0.2 mg/mL catalase in 50 mM potassium phosphate buffer (pH 6.5). The initial reaction rates were recorded by continuously following the absorbance increase at 321 nm due to the formation of N’-formlylkynurenine. Cell Assay: In Hela cells, INCB024360 analogue selectively inhibited the activity of human IDO1 with an IC50 value of 19 nM. In murine B16 cells, INCB024360 analogue inhibited IDO with an IC50 value of 46 NM. |
|---|---|
| In Vivo | In mice bearing GM-CSF-secreting B16 tumors, INCB024360 (75 mg/kg b.i.d) causes dose dependent inhibition of tumor growth. INCB024360 significantly suppresses tumor growth in immunocompetent, but not immunodeficient, mice. |
| Animal model | Mice bearing GM-CSF-secreting B16 tumors |
| Formulation & Dosage | Dissolved in 5% DMA, 47.5% propylene glycol; 75 mg/kg; s.c. administration |
| References | J Med Chem. 2009 Dec 10;52(23):7364-7; Blood. 2010 Apr 29;115(17):3520-30. |
