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| Targets |
TIM-3-IN-1 targets TIM-3, an immune checkpoint receptor expressed on T cells, particularly on exhausted T cells in the tumor microenvironment. As an inhibitor, it blocks TIM-3 signaling, which is known to suppress T-cell activation and promote T-cell exhaustion. By inhibiting TIM-3, this compound aims to reinvigorate T-cell function. It is a TIM-3 inhibitor that can be used for the research of cancer.
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| ln Vitro |
Specific in vitro activity data for TIM-3-IN-1, such as IC50 or KD values, is not provided in standard chemical databases. However, it is described as a TIM-3 inhibitor that can be used for the research of cancer. As a research tool, it is expected to block TIM-3 interactions with its ligands (Gal-9, PtdSer, CEACAM1), thereby reversing T-cell exhaustion and enhancing cytokine production (IL-2, IFN-gamma, TNF-alpha) in T-cell activation assays.
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| ln Vivo |
Specific in vivo activity data for TIM-3-IN-1 has not been published. It represents a useful tool for further investigation of the biology of TIM-3 immunomodulation in cancer. Based on its mechanism, it is hypothesized to inhibit tumor growth in syngeneic mouse models (e.g., CT26, MC38, B16-F10) by enhancing CD8+ T-cell infiltration and function, and may show synergistic effects with PD-1/PD-L1 inhibitors.
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| Enzyme Assay |
The specific protocol for evaluating TIM-3-IN-1 binding would involve a surface plasmon resonance (SPR) or microscale thermophoresis (MST) binding assay. Recombinant human TIM-3 protein is immobilized on a sensor chip. TIM-3-IN-1 is serially diluted (0.01 uM to 100 uM) and injected over the chip. Association and dissociation kinetics are monitored. KD values are determined by fitting the sensorgrams to a 1:1 binding model. Alternatively, a competition ELISA can be performed using immobilized TIM-3 and biotinylated Gal-9.
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| Cell Assay |
For in vitro cellular assays, primary human CD8+ T cells are isolated from healthy donor PBMCs using magnetic negative selection. T cells are activated with anti-CD3/CD28 beads (1:1 ratio) and cultured in the presence of TIM-3 ligand-expressing cells (e.g., Gal-9-expressing L cells). TIM-3-IN-1 is added at concentrations of 1, 5, 10, and 20 uM. After 72 hours, cell culture supernatants are collected for IFN-gamma and IL-2 quantification by ELISA. T-cell proliferation is assessed by [3H]-thymidine incorporation during the final 18 hours of culture. The ability of TIM-3-IN-1 to rescue T-cell function is measured as increased proliferation and cytokine production compared to control.
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| Animal Protocol |
An in vivo protocol for TIM-3-IN-1 would involve the MC38 syngeneic colon carcinoma model in C57BL/6 mice. Mice are implanted subcutaneously with 5×10⁵ MC38 cells. When tumors reach 50-100 mm3, mice are randomized into groups. TIM-3-IN-1 is administered intraperitoneally at doses of 5-30 mg/kg in a formulation such as 10% DMSO/40% PEG400/50% saline, given daily or every other day for 14 days. Anti-PD-1 antibody (10 mg/kg, i.p.) can be administered in combination groups. Tumor volumes are measured every 2-3 days with calipers. At termination, tumors are collected for flow cytometry analysis of CD8+ T-cell infiltration and exhaustion markers (TIM-3, PD-1, LAG-3).
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| ADME/Pharmacokinetics |
Detailed PK data for TIM-3-IN-1 is not available. As a small molecule inhibitor, a standard oral PK study in C57BL/6 mice would be conducted. TIM-3-IN-1 would be administered at 10 mg/kg by oral gavage. Blood samples would be collected at multiple time points up to 24 hours. Plasma concentrations would be determined by LC-MS/MS. Key parameters including T1/2, Cmax, Tmax, AUC, and oral bioavailability would be calculated.
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| Toxicity/Toxicokinetics |
Specific toxicology data for TIM-3-IN-1 is not available. As an immune checkpoint inhibitor, the primary safety concern is immune-related adverse events (irAEs). These could include immune-mediated pneumonitis, colitis, hepatitis, and dermatitis due to non-specific T-cell activation. Standard safety assessment would include in vitro hERG channel testing, CYP450 inhibition screening, and a 7-day repeat-dose toxicity study in mice to determine the maximum tolerated dose (MTD).
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| References | |
| Additional Infomation |
TIM-3-IN-1 (Compound 38) is a research-grade chemical and is not approved for clinical use. Its molecular weight is 469.90, with a molecular formula of C20H16ClN7O3S and a purity of 99.15%. It is a useful tool to enable further studies on the biology of TIM-3 immunoregulation in cancer. It can be used for the research of cancer, particularly in combination with other immune checkpoint inhibitors. It is stored as a powder at -20degC.
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| Molecular Formula |
C20H16CLN7O3S
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| Molecular Weight |
469.904140472412
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| Exact Mass |
469.072
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| CAS # |
2883237-04-3
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| PubChem CID |
156613413
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
827
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC(=C1)NS(=O)(=O)C2=NC=CN2)C3=C(C=C4C(=C3)C5=NC(=NN5C(=O)N4)C)Cl
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| InChi Key |
MJDFVGVHKKUOFT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H16ClN7O3S/c1-10-7-12(27-32(30,31)19-22-5-6-23-19)3-4-13(10)14-8-15-17(9-16(14)21)25-20(29)28-18(15)24-11(2)26-28/h3-9,27H,1-2H3,(H,22,23)(H,25,29)
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| Chemical Name |
N-[4-(8-chloro-2-methyl-5-oxo-6H-[1,2,4]triazolo[1,5-c]quinazolin-9-yl)-3-methylphenyl]-1H-imidazole-2-sulfonamide
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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: 100 mg/mL (212.81 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1281 mL | 10.6406 mL | 21.2811 mL | |
| 5 mM | 0.4256 mL | 2.1281 mL | 4.2562 mL | |
| 10 mM | 0.2128 mL | 1.0641 mL | 2.1281 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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