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| 1mg |
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| 5mg |
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| Targets |
Indoleamine-2,3-dioxygenase (IDO). (R)-IDO/TDO-IN-1 (compound 25) is an IDO inhibitor. It blocks the rate-limiting enzyme in the kynurenine pathway of tryptophan catabolism. Reversing IDO-mediated tryptophan depletion and kynurenine accumulation in the tumor microenvironment can relieve immunosuppression and restore anti-tumor T-cell responses.
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| ln Vitro |
In cell-free enzyme assays, (R)-IDO/TDO-IN-1 directly inhibits IDO activity. It demonstrates good pharmacokinetic properties in vitro. In the MC38 colon carcinoma cell line, it likely restores T-cell proliferation by preventing tryptophan depletion and reducing kynurenine production. The compound also shows synergy with anti-PD-1 monoclonal antibodies, enhancing the activation of cytotoxic T lymphocytes (CTLs).
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| ln Vivo |
In vivo, (R)-IDO/TDO-IN-1 exerts anti-tumor effects in the MC38 syngeneic colon carcinoma xenograft model. Oral administration leads to reduced tumor growth and enhanced immune cell infiltration. It displays a synergistic anti-tumor effect when combined with an anti-PD-1 monoclonal antibody (SHR-1210), indicating that blocking the IDO pathway can improve the efficacy of checkpoint inhibitor immunotherapy.
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| Enzyme Assay |
For cell-free IDO inhibition assays, purified human IDO-1 enzyme is incubated with L-tryptophan in the presence of catalase and methylene blue. (R)-IDO/TDO-IN-1 is added at varying concentrations (0.1-100 uM). The reaction is quenched, and the production of kynurenine is measured by absorbance at 480 nm using Ehrlich's reagent. IC50 values are calculated from the dose-response curves.
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| Cell Assay |
For T-cell functional assays, CD8+ T-cells are co-cultured with IDO-expressing tumor cells (e.g., MC38). (R)-IDO/TDO-IN-1 is added to the co-culture medium (0.5-10 uM). After 72 hours, T-cell proliferation is measured by CFSE dilution, and cytokine secretion (IFN-gamma, TNF-alpha) is measured by ELISA. Kynurenine levels in the supernatant are quantified by HPLC-MS to confirm on-target activity.
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| Animal Protocol |
For efficacy studies, (R)-IDO/TDO-IN-1 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or 10% DMSO in PBS) and administered orally to MC38 tumor-bearing mice. Doses and schedules are optimized in the literature. Tumor volume is measured bi-weekly. At study termination, tumors and spleens are harvested for flow cytometry analysis of immune cell populations (e.g., CD8+ T-cells, Tregs). Plasma is collected to measure tryptophan and kynurenine levels via LC-MS/MS as a pharmacodynamic marker.
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| ADME/Pharmacokinetics |
(R)-IDO/TDO-IN-1 has a molecular weight of 413.49 g/mol and a molecular formula of C25H24FN5. It is the R-enantiomer of an IDO/TDO inhibitor and is noted for its good pharmacokinetic properties. It is soluble in DMSO. While specific PK parameters (t1/2, Cmax, F%) are described as "good" in the literature, detailed values are available in patent documents. The compound is stored as a powder at -20degC.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for (R)-IDO/TDO-IN-1 are not fully published in the abstract search results. As a research compound, it is not intended for human use. Standard preclinical toxicology studies would be required for development, but currently, it is a chemical probe. However, its mechanism of action is immune modulation, which carries a potential risk for immune-related adverse events such as colitis, pneumonitis, or hepatitis, similar to checkpoint inhibitors.
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| References | |
| Additional Infomation |
(R)-IDO/TDO-IN-1 (compound 25) is a representative of a class of IDO inhibitors that have been intensely pursued for cancer immunotherapy. While early IDO inhibitors like epacadostat failed in Phase III clinical trials due to lack of efficacy as monotherapy, combination strategies (with PD-1 blockers) remain an active area of research. This compound is a research tool to explore such combinations. It is not an FDA-approved drug.
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| Molecular Formula |
C25H24FN5
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| Molecular Weight |
413.489968299866
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| Exact Mass |
413.201
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| CAS # |
2033173-00-9
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| Related CAS # |
IDO/TDO-IN-1;2033173-01-0
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| PubChem CID |
122650368
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
617
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C=C(C=N1)C2=CC=C(C=C2)N3CCC(CC3)[C@@H]4C5=C(C=CC=C5F)C6=CN=CN46
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| InChi Key |
UJGQDAMZVUNFBQ-RUZDIDTESA-N
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| InChi Code |
InChI=1S/C25H24FN5/c1-29-15-19(13-28-29)17-5-7-20(8-6-17)30-11-9-18(10-12-30)25-24-21(3-2-4-22(24)26)23-14-27-16-31(23)25/h2-8,13-16,18,25H,9-12H2,1H3/t25-/m1/s1
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| Chemical Name |
(5R)-6-fluoro-5-[1-[4-(1-methylpyrazol-4-yl)phenyl]piperidin-4-yl]-5H-imidazo[5,1-a]isoindole
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 10 mg/mL (24.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 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. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4184 mL | 12.0922 mL | 24.1844 mL | |
| 5 mM | 0.4837 mL | 2.4184 mL | 4.8369 mL | |
| 10 mM | 0.2418 mL | 1.2092 mL | 2.4184 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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