| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
IDO1 (IC50 = 3.53 μM); TDO (IC50 = 1.15 μM); kynurenine pathway; tryptophan catabolism.
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|---|---|
| ln Vitro |
According to morphological alterations, LPS-induced BV2 microglial activation is inhibited by IDO1/TDO-IN-4 (Compound 28, 0-2 μM, 1 hour) [1]. IDO1/TDO-IN-4 (0-2 μM, 1 h) stimulates the expression of IL-10 while suppressing the synthesis of pro-inflammatory factors [1]. IDO1/TDO-IN-4 (0-2 μM, 1 hour) inhibits the over-degradation of tryptophan via the kynurenine pathway and lowers IDO1 expression [1].
IDO1/TDO-IN-4 inhibits IDO1 with an IC50 of 3.53 μM and TDO with an IC50 of 1.15 μM, demonstrating dual activity with approximately 3-fold preference for TDO. It blocks tryptophan catabolism and reduces kynurenine production in cells. It is a tool for studying the kynurenine pathway and a lead for cancer immunotherapy. |
| ln Vivo |
Compound 28, administered intraperitoneally at a dose of 20 mg/kg on days 1, 2, and 3, has the ability to rescue mice from LPS-induced neuroinflammation and depressive-like behavior [1]. In normal mice, the intravenous injection (20 mg/kg) of IDO1/TDO-IN-4 shows a high steady-state volume of distribution and high exposure [1].
In vivo, dual IDO1/TDO inhibition is expected to restore antitumour immune responses by reducing kynurenine levels and increasing tryptophan availability. Rodent studies would use oral or intraperitoneal dosing (e.g., 10–100 mg/kg) in tumour models and measure plasma kynurenine/tryptophan ratios, tumour growth, and immune cell infiltration. |
| Enzyme Assay |
For IDO1 and TDO enzyme assays, purified enzymes are incubated with L-tryptophan, a cofactor (e.g., methylene blue for IDO1), and serially diluted IDO1/TDO-IN-4. Kynurenine production is measured spectrophotometrically at 480 nm after Ehrlich’s reagent addition, and IC50 is derived from dose-response curves.
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| Cell Assay |
RT-PCR[1]
Cell Types: 100 ng/mL LPS-induced BV2 microglia Tested Concentrations: 0, 0.25, 0.5, 1, 2 μM Incubation Duration: 1 h Experimental Results: Inhibition of COX2, iNOS, TNF-α, and IL-1β. IL-10 levels are elevated. For cell-based assays, cancer cells expressing IDO1 or TDO (e.g., IFN-γ-stimulated cancer cells) are treated with IDO1/TDO-IN-4 (0.1–100 μM), and kynurenine levels in culture supernatants are measured by ELISA or HPLC. Tryptophan consumption is quantified by LC-MS. |
| Animal Protocol |
Animal/Disease Models: 2 mg/kg LPS-induced depression in mice [1]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection, days 1, 2, and 3. Experimental Results: Microglial activation was Dramatically attenuated. Hippocampal inflammatory factors were diminished, such as TNF-α, IL-1β, and iNOS. Downregulates LPS-induced IDO1 overexpression. Animal/Disease Models: Male C57BL/6J mice (pharmacokinetic/PK/PK determination) [1] Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection and intravenous (iv) (iv)injection Experimental Results: IDO1/TDO-IN-4 (compound 28) pharmacokinetic/PK/PKs Chemical properties T1/2 (h) Tmax (h) Cmax (ng/mL) Bioavailability F (%) iv/ip 2.31/0.77 0.25 5543.99/3878 52.55 For in vivo studies, mice bearing IDO1/TDO-expressing tumours receive IDO1/TDO-IN-4 (e.g., 10–100 mg/kg/day, oral or i.p.) for 2–4 weeks. Plasma kynurenine/tryptophan ratios are measured by LC-MS/MS, and tumour growth and immune cell infiltration (CD8+ T cells, Tregs) are assessed by flow cytometry and immunohistochemistry. |
| References |
| Molecular Formula |
C14H10N4
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|---|---|
| Molecular Weight |
234.26
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| Exact Mass |
234.09
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| CAS # |
461424-21-5
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| PubChem CID |
44269517
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| Appearance |
Yellow to brown solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
308
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C=C2C(NC3C2=CC=NC=3C2=CN=CN2)=CC=1
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| InChi Key |
HUTBKGSJEGKJBG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H10N4/c1-2-4-11-9(3-1)10-5-6-16-14(13(10)18-11)12-7-15-8-17-12/h1-8,18H,(H,15,17)
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| Chemical Name |
1-(1H-imidazol-5-yl)-9H-pyrido[3,4-b]indole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~533.60 mM)
MEthanol : ~16.67 mg/mL (~71.16 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (8.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2688 mL | 21.3438 mL | 42.6876 mL | |
| 5 mM | 0.8538 mL | 4.2688 mL | 8.5375 mL | |
| 10 mM | 0.4269 mL | 2.1344 mL | 4.2688 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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