INCB-024360 (Synonyms: INCB024360) |
| Catalog No.GC17968 |
INCB-024360(INCB 024360)은 IC50이 71.8nM인 강력하고 선택적인 인돌아민 2,3-디옥시게나제 1(IDO1) 억제제입니다.
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Cas No.: 1204669-58-8
Sample solution is provided at 25 µL, 10mM.
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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.
| 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. | |
| Cas No. | 1204669-58-8 | SDF | |
| Synonyms | INCB024360 | ||
| 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 |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 | 1.141 mL | 2.2819 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)
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