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| Targets |
DMA-135 HCl targets the internal ribosome entry site (IRES) of enteroviruses, including enterovirus 71 (EV71). The IRES is a structured RNA element that mediates cap-independent translation of viral RNA. By binding to the SLII domain of the EV71 IRES with moderately high affinity (Kd = 520 nM), DMA-135 HCl inhibits IRES-dependent translation and replication of the virus. This mechanism of action makes it a promising antiviral agent for the treatment of enteroviral infections, including hand, foot, and mouth disease and neurological complications associated with EV71.
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| ln Vitro |
In vitro, DMA-135 HCl binds to the SLII domain of EV71 with moderately high affinity (Kd = 520 nM). The compound inhibits EV71 IRES-dependent translation and replication in cell-based assays. Its antiviral activity is concentration-dependent, with effective concentrations typically in the micromolar range. DMA-135 HCl shows no significant toxicity in cell-based studies, indicating a favorable selectivity index. Its RNA-targeting mechanism makes it a valuable tool for studying RNA-mediated viral replication and for developing novel antiviral therapeutics.
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| ln Vivo |
In vivo, DMA-135 HCl has been studied in preclinical models of enterovirus infection. Its ability to inhibit EV71 replication may reduce viral load and disease severity. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying RNA-targeting antiviral strategies. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
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| Enzyme Assay |
The in vitro IRES binding assay for DMA-135 HCl typically uses RNA-binding assays such as surface plasmon resonance (SPR) or fluorescence polarization to measure binding to the EV71 SLII domain. The assay is performed with varying concentrations of the test compound (typically 1 nM to 10 µM) and the RNA target. The dissociation constant (Kd) is calculated from the binding curves using appropriate mathematical models. For antiviral activity assays, cells infected with EV71 are treated with varying concentrations of the compound, and viral replication is measured by qRT-PCR or plaque assay. Cell viability is assessed using MTT or CellTiter-Glo assays. Positive controls and negative controls are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cells infected with EV71 or other enteroviruses are treated with DMA-135 HCl at concentrations ranging from 0.1 to 100 µM for 24-72 hours. Viral RNA levels are measured by qRT-PCR. Viral titers are determined by plaque assay or TCID50. IRES-dependent translation is assessed using a dual-luciferase reporter assay with IRES-containing constructs. Cell viability is assessed using MTT or CellTiter-Glo assays to evaluate cytotoxicity. All experiments include appropriate controls (vehicle, untreated infected cells) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, rodent models of EV71 infection are used. DMA-135 HCl is administered via intraperitoneal injection or oral gavage at doses ranging from 1 to 50 mg/kg, typically once or twice daily. Viral load is measured in tissues by qRT-PCR. Disease severity is assessed by clinical scoring and histology. Survival is monitored. All animal procedures should be conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of DMA-135 HCl have been partially characterized. The compound has a molecular weight of 359.81 and a molecular formula of C16H18ClN7O. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including liver and kidney. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of DMA-135 HCl indicate no significant toxicity in cell-based studies. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
DMA-135 HCl is a small-molecule antiviral agent targeting the EV71 IRES (Kd = 520 nM). It inhibits EV71 IRES-dependent translation and replication. The compound has no significant toxicity in cell-based studies. It is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥98%) for laboratory use only. Its RNA-targeting mechanism makes it a valuable tool for studying RNA-mediated viral replication and for developing novel antiviral therapeutics.
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| Molecular Formula |
C16H18CLN7O
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| Molecular Weight |
359.81
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| Exact Mass |
359.126
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| CAS # |
2237925-62-9
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| PubChem CID |
163196482
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
537
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N=C(N)NC(C1N=C(C#CC2C=CC=CC=2)C(N(C)C)=NC=1N)=O.Cl
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| InChi Key |
RBMSZKWMVJWPEP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H17N7O.ClH/c1-23(2)14-11(9-8-10-6-4-3-5-7-10)20-12(13(17)21-14)15(24)22-16(18)19;/h3-7H,1-2H3,(H2,17,21)(H4,18,19,22,24);1H
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| Chemical Name |
3-amino-N-(diaminomethylidene)-5-(dimethylamino)-6-(2-phenylethynyl)pyrazine-2-carboxamide;hydrochloride
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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, avoid exposure to moisture. |
| 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 (~138.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.90 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 50.0 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: ≥ 5 mg/mL (13.90 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7792 mL | 13.8962 mL | 27.7924 mL | |
| 5 mM | 0.5558 mL | 2.7792 mL | 5.5585 mL | |
| 10 mM | 0.2779 mL | 1.3896 mL | 2.7792 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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