| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
The compound targets a histone methyltransferase (HMT) in the malaria parasite Plasmodium falciparum. This enzyme plays a critical role in the epigenetic regulation of gene expression. TM2-115 shows high selectivity for the parasite enzyme over the closest human homolog, G9a (IC50 >1,000 nM), indicating a strong species-specific mechanism of action.
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| ln Vitro |
TM2-115 is a highly selective inhibitor of P. falciparum HMT, with an IC50 of 43 nM. By inhibiting the parasite's histone methyltransferase, the compound disrupts essential epigenetic regulation, resulting in rapid and irreversible parasite death. Its selectivity is over 23-fold greater for the parasite HMT compared to the human HMT G9a (IC50 >1 uM), suggesting a favorable safety margin.
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| ln Vivo |
Specific in vivo efficacy data for TM2-115 is not detailed. As a potent antimalarial compound, its in vivo activity would be evaluated in a P. berghei or P. falciparum mouse malaria model (e.g., using NSG mice engrafted with human red blood cells). Mice would be treated with TM2-115 (e.g., orally or intraperitoneally) once daily for 4 days. Parasitemia levels would be monitored by blood smear and flow cytometry to calculate the compound's ED50 and ED90.
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| Enzyme Assay |
A biochemical methylation assay is used to evaluate inhibition. Purified recombinant P. falciparum histone methyltransferase is incubated with a histone H3 peptide substrate, the methyl donor SAM, and varying concentrations of TM2-115. After incubation, the amount of methylated histone peptide (e.g., H3K4 or H3K9) is measured using a homogeneous time-resolved fluorescence (HTRF) or AlphaScreen assay with specific antibodies. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
P. falciparum parasites (e.g., the 3D7 strain) are cultured in vitro in human red blood cells. Parasite cultures are treated with varying concentrations of TM2-115 for 48-72 hours. The percentage of parasitemia is measured by flow cytometry using a nucleic acid dye (e.g., SYBR Green I) or by microscopic examination of Giemsa-stained blood smears. The IC50 for parasite growth inhibition is then calculated. The compound's rapid parasite-killing kinetics can be assessed by measuring ring-stage parasite survival.
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| Animal Protocol |
Specific in vivo protocols are not detailed. A standard antimalarial efficacy model is the Peters' 4-day suppressive test. Female BALB/c mice are infected intraperitoneally with P. berghei (ANKA strain) parasitized erythrocytes (e.g., 1 × 10⁶ cells). TM2-115 is administered (e.g., orally or intraperitoneally) daily for 4 days starting 2 hours post-infection. On day 4, blood smears are collected and the percentage of parasitemia is determined. The compound's ability to prevent the development of the parasite is calculated as percent suppression.
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| ADME/Pharmacokinetics |
Specific PK parameters for TM2-115 are not detailed. As a small molecule (MW 490.64) with potential antimalarial activity, it is expected to be orally bioavailable to be an effective therapeutic. Key properties for an antimalarial include good absorption, a long half-life to prevent recrudescence, and high tissue penetration to reach parasites sequestered in organs like the spleen.
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| Toxicity/Toxicokinetics |
Specific toxicological data for TM2-115 is not detailed in the literature. However, its high selectivity (>23-fold) for the parasite enzyme over the closest human homolog (G9a) suggests it may have a favorable safety profile. Standard toxicological endpoints for an antimalarial would include hematological parameters, liver and kidney function, and histopathological analysis of major organs in animal models.
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| Additional Infomation |
TM2-115 is a research-grade chemical tool for studying the role of histone methyltransferases in malaria biology. As antimalarial resistance to current therapies (e.g., artemisinin) continues to spread, the development of compounds with novel mechanisms of action, such as epigenetic inhibition, is a high priority. As of the latest updates, TM2-115 is a pre-clinical compound and has not yet been approved for clinical use.
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| Molecular Formula |
C28H38N6O2
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|---|---|
| Molecular Weight |
490.640326023102
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| Exact Mass |
490.306
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| CAS # |
1197196-47-6
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| PubChem CID |
44607518
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
656
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCCN(CC1)C2=NC3=CC(=C(C=C3C(=N2)NC4CCN(CC4)C)OC)OCC5=CC=CC=C5
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.0382 mL | 10.1908 mL | 20.3815 mL | |
| 5 mM | 0.4076 mL | 2.0382 mL | 4.0763 mL | |
| 10 mM | 0.2038 mL | 1.0191 mL | 2.0382 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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