| INCB-024360potent and selective inhibitor of IDO1 |
Sample solution is provided at 25 µL, 10mM.
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Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 99.10%
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Chemical structure
| Description | INCB024360 is a potent inhibitor of IDO1 with an IC50 value of 10 nM. | |||||
| Targets | IDO1 | |||||
| IC50 | 10 nM | |||||
| Kinase experiment [1]: | |
Kinase assays | 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 experiment [2]: | |
Cell lines | HeLa cells and human T cells |
Preparation method | The solubility of this compound in DMSO is >15.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | 0.001~2 μM |
Applications | IDO1 induction significantly suppressed T-cell proliferation in coculture systems, and the suppression was effectively reversed by INCB024360. IDO1 also increases IFN-γ production, and reduces conversion to regulatory T (Treg)–like cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice bearing IDO1-expressing PAN02 pancreatic carcinomas |
Dosage form | 25 and 100 mg/kg, orally, twice a day for 25 days |
Application | The growth of tumors in syngeneic immunocompetent C57BL/6 mice was inhibited in a dose-dependent fashion. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1] Yue EW1, Douty B, Wayland B, et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. Med Chem. 2009 Dec 10;52(23):7364-7. [2] Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M et al: Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30. | |
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| Cas No. | 1204669-58-8 | SDF | Download SDF |
| Chemical Name | (E)-N"-(3-bromo-4-fluorophenyl)-N-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide | ||
| Canonical SMILES | BrC1=C(F)C=CC(/N=C(NO)C2=NON=C2NCCNS(N)(=O)=O)=C1 | ||
| Formula | C11H13BrFN7O4S | M.Wt | 438.23 |
| Solubility | ≥17.1mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
INCB024360 is a potent and selective inhibitor of IDO1 with IC50 value of 10 nM. [1]IDO means indoleamine-pyrrole 2, 3-dioxygenase. IDO is an enzyme which is encoded by the IDO1 gene. IDO is the rate-limiting and first enzyme of tryptophan which is one amino acid of human catabolism through kynurenine pathway. The decrease of L-tryptophan can cause halted growth of T cells as well as microbes. IDO belongs to immunomodulatory enzyme. It is produced by some activated macrophages and immunoregulatory cells. IDO is overexpressed in a wide range of cancer cells such as lung, prostatic, pancreatic, colorectal cancer. It is indentified to help cancer cells to escape the immune system by reducing the level of L-tryptophan in the microenvironment of cells.[2]In Hela cells, INCB024360 selectively inhibits the activity of human IDO1 with IC50 values of about 10nM. On the other hand INCB024360demonstrates little inhibition activity against human IDO1 or TDO (tryptophan 2, 3-dioxygenase). In coculture systems of human dendritic cells with allogeneic lymphocytes, INCB024360 inhibit T-cell proliferation and cytokine production and influence the viability of NK cells. INCB024360 also increase CD86 expression and promote activation T cells by DCs. In mice bearing IDO1-expressing PAN02 pancreatic tumour, ICB024360 significantly inhibit tumour growth in lymphocyte-dependent manner.[1] INCB024360 decreased plasma kynurenine levels by inhibiting the activity of IDO1 at 50 mg/kg in native C57BL/6 mice. INCB024360 also inhibit tumor growth at 100mg/kg in CT26 tumor bearing mice.[3]References: [1]. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M et al: Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood, 115(17):3520-3530.[2]. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003, 9(10):1269-1274.[3]. Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW et al: Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther, 9(2):489-498.
