| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
LM10 targets tryptophan 2,3-dioxygenase (TDO), an enzyme primarily expressed in the liver but also found in various tumors. TDO catalyzes the conversion of tryptophan to N-formylkynurenine, the first step in the kynurenine pathway. This pathway is a major mechanism of immune suppression in the tumor microenvironment, as the depletion of tryptophan and the accumulation of its immunosuppressive metabolites inhibit T cell proliferation and function. LM10 acts as a potent and selective inhibitor of TDO, with IC50 values of 0.62 μM for human TDO and 2 μM for mouse TDO. By inhibiting TDO, LM10 prevents the degradation of tryptophan, thereby reversing the immunosuppressive environment and enhancing the body's immune response against cancer cells.
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| ln Vitro |
In vitro, LM10 is a potent inhibitor of TDO enzymatic activity. In HEK293 cells expressing TDO, LM10 inhibits the enzyme with an IC50 of 0.398 μM when using L-tryptophan as a substrate. This potent inhibition prevents the depletion of tryptophan and the production of immunosuppressive kynurenine metabolites. The compound's selectivity for TDO over the related enzyme indoleamine 2,3-dioxygenase (IDO) is a key feature, as it allows for specific modulation of the TDO pathway without affecting IDO-mediated tryptophan metabolism. These in vitro activities confirm LM10's mechanism as a selective TDO inhibitor with potential for restoring anti-tumor immunity.
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| ln Vivo |
Oral LM10 (160 mg/kg) inhibits the development of P815 tumor cells that express TDO and enhances the rejection of the TDO-negative control clone P815B cl1 [1]. Good competitive inhibition characteristics and TDO inhibition (Ki = 5.6 μM) are demonstrated by LM10 [1]. LM10 exhibits no overt toxicity indicators, is highly soluble and bioavailable, and does not inhibit IDO [1]. After taking 160 mg/kg/day orally, plasma concentrations of LM10 varied between 20 and 40 μg/mL (87-175 μM). This is roughly 40 times greater than the IC50 found in cellular experiments employing physiological tryptophan plasma values [1].
In vivo, LM10 has demonstrated anti-neoplastic activity in a murine syngeneic tumor model. By inhibiting TDO, the compound reverses the immune tolerance that allows tumor cells to evade immune system detection and destruction. This leads to the restoration of anti-tumor immune responses, resulting in reduced tumor growth. The compound's in vivo efficacy supports its potential as a therapeutic agent for cancer immunotherapy. Detailed in vivo efficacy data, including specific tumor models and dosing regimens, are not extensively reported in the available literature. |
| Enzyme Assay |
Non-cell-based enzyme assays for LM10 use purified TDO enzyme or recombinant TDO expressed in cell lines. The compound is incubated with the enzyme, its substrate L-tryptophan, and cofactors such as heme and ascorbate at varying concentrations. TDO activity is measured by quantifying the production of N-formylkynurenine or its downstream metabolite kynurenine using spectrophotometric, fluorometric, or HPLC methods. IC50 values for enzyme inhibition are determined from dose-response curves. Selectivity profiling against IDO and other related enzymes is performed to confirm specificity.
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| Cell Assay |
Cellular assays for LM10 utilize cells expressing TDO, such as HEK293 cells transfected with TDO. Cells are treated with the compound at various concentrations for a specified duration (e.g., 8 hours) in the presence of L-tryptophan. The levels of tryptophan and kynurenine in the culture supernatant are measured by HPLC or LC-MS to assess TDO inhibition. Alternatively, the functional consequences of TDO inhibition can be assessed in co-culture systems with immune cells, where the compound's ability to restore T cell proliferation or cytokine production is measured.
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| Animal Protocol |
Animal/Disease Models: DBA/2 mice (6-8 weeks) [1]
Doses: 160 mg/kg/day Route of Administration: Oral Experimental Results: Prevented the growth of TDO-expressing P815 tumor cells and promoted growth of control clone P815B cl1 Good exclusion, does not express TDO. In vivo animal models for LM10 include syngeneic tumor models in immunocompetent mice. Tumor cells are implanted, and once tumors are established, LM10 is administered via appropriate routes (e.g., oral gavage or intraperitoneal injection) at various doses. Tumor growth is monitored by caliper measurements. To assess the immune-mediated mechanism, tumor-infiltrating lymphocytes (TILs) are analyzed by flow cytometry to measure T cell frequency and activation status. Tryptophan and kynurenine levels in tumor tissues or plasma are measured to confirm target engagement. Detailed protocols are not extensively reported. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LM10 include CAS number 1316695-35-8. The compound is a small molecule TDO inhibitor. It is supplied as a solid and is soluble in DMSO. Purity is not specified but is of research grade. Detailed PK parameters such as molecular weight, half-life, bioavailability, and volume of distribution are not extensively reported in the available literature. The compound is a research reagent for laboratory use only.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for LM10 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only. Given its mechanism of TDO inhibition, potential effects on tryptophan metabolism and immune function in normal tissues would be key safety considerations.
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| References | |
| Additional Infomation |
LM10 is a potent and selective inhibitor of tryptophan 2,3-dioxygenase (TDO). It has CAS number 1316695-35-8. LM10 inhibits human TDO with an IC50 of 0.62 μM and mouse TDO with an IC50 of 2 μM. By inhibiting TDO, it reverses the immune tolerance that permits tumor cells to evade immune system detection and destruction. It has demonstrated anti-neoplastic activity in a murine syngeneic tumor model. It is used as a research tool for studying cancer immunology and as a lead compound for immunotherapy development.**
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| Molecular Formula |
C11H8FN5
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| Molecular Weight |
229.2131
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| Exact Mass |
229.076
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| CAS # |
1316695-35-8
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| PubChem CID |
135743630
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
522.5±60.0 °C at 760 mmHg
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| Flash Point |
269.8±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.829
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
298
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC2=C(C=C1F)NC=C2/C=C/C3=NNN=N3
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| InChi Key |
JDBSZVDIUIRSDG-DAFODLJHSA-N
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| InChi Code |
InChI=1S/C11H8FN5/c12-8-2-3-9-7(6-13-10(9)5-8)1-4-11-14-16-17-15-11/h1-6,13H,(H,14,15,16,17)/b4-1+
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| Chemical Name |
6-fluoro-3-[(E)-2-(1H-1,2,3,4-tetrazol-5-yl)ethenyl]-1H-indole
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| Synonyms |
LM10 LM 10 LM-10.
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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 : ~50 mg/mL (~218.14 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.91 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (10.91 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 25.0 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: 16.67 mg/mL (72.73 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 16 mg/mL (69.80 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3628 mL | 21.8141 mL | 43.6281 mL | |
| 5 mM | 0.8726 mL | 4.3628 mL | 8.7256 mL | |
| 10 mM | 0.4363 mL | 2.1814 mL | 4.3628 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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