| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
PD-404182 targets multiple enzymes. Its primary target is DDAH1, an enzyme that metabolizes asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS). By inhibiting DDAH1, PD-404182 elevates intracellular ADMA levels, which in turn reduces nitric oxide (NO) production. This mechanism is relevant to cardiovascular research. The compound also inhibits KDO 8-P synthase, an enzyme involved in the biosynthesis of lipopolysaccharide (LPS) in Gram-negative bacteria. Additionally, it exhibits antiviral activity, suggesting it may interact with viral or host factors involved in viral replication.
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| ln Vitro |
Asymmetric dimethylarginine (ADMA) in EC is increased by around 70% in response to PD 404182 (20 μM) [1]. In vitro, PD 404182 (50-100 μM; 18 hours) reduces endothelial tube formation without compromising the integrity of cell membranes or causing cytotoxicity [1]. With an IC50 of 1 μM, PD 404182 suppresses HIV-1 in seminal plasma[2]. When applied to various human cell lines, freshly activated PBMCs, primary CD4+ T lymphocytes, macrophages, dendritic cells, and lactobacilli in the normal vaginal flora, PD 404182 (300 μM; 30 min) shows minimal toxicity [2].
In vitro, PD-404182 has been shown to significantly increase intracellular levels of ADMA in cultured primary human vascular endothelial cells. At a concentration of 20 μM, it increases ADMA levels by approximately 70%. The compound also reduces LPS-induced NO production. It inhibits endothelial tube formation at concentrations of 50-100 μM without compromising cell membrane integrity or causing significant cytotoxicity. PD-404182 suppresses HIV-1 replication in seminal plasma with an IC50 of 1 μM and shows minimal toxicity in various human cell lines and primary cells at concentrations up to 300 μM. |
| ln Vivo |
In vivo, PD-404182 is being investigated for its potential therapeutic applications. Its ability to modulate the ADMA/DDAH/NO pathway makes it a candidate for studying cardiovascular diseases, where endothelial dysfunction and impaired NO production are key features. Its antiviral activity suggests potential for the treatment of viral infections, including HIV-1 and herpes simplex virus. However, specific in vivo efficacy data from animal models are less detailed in the available literature. The compound is primarily used as a research tool to investigate these pathways.
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| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for PD-404182 involve measuring its inhibition of DDAH1 enzymatic activity. The assay uses a purified recombinant DDAH1 enzyme and a substrate, such as ADMA or a synthetic analogue. The enzymatic activity is monitored by measuring the production of citrulline or by using a coupled assay. The compound is incubated with the enzyme and substrate at varying concentrations, and the IC50 or Ki is determined from the inhibition curve. For PD-404182, an IC50 of 9 μM for DDAH1 and a Ki of 26 nM for KDO 8-P synthase have been reported.
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| Cell Assay |
Cell viability assay [1]
Cell Types: Human dermal microvascular endothelial cells (EC) Tested Concentrations: 10-300 μM Incubation Duration: 24 hrs (hours) Experimental Results: No cytotoxicity is induced. In vitro cell-based assays for PD-404182 are performed using primary human vascular endothelial cells (ECs) or other relevant cell lines. Cells are treated with the compound, and intracellular ADMA levels are measured using liquid chromatography-mass spectrometry (LC-MS) or ELISA. Nitric oxide (NO) production is assessed by measuring nitrite levels in the culture medium using the Griess assay. The antiangiogenic activity is evaluated using endothelial tube formation assays on Matrigel. Antiviral activity is assessed by infecting cells with HIV-1 or herpes simplex virus in the presence of the compound and measuring viral replication. Cytotoxicity is evaluated using standard cell viability assays. |
| Animal Protocol |
In vivo animal experiments for PD-404182 are conducted using mouse models of cardiovascular disease or viral infection. The compound is administered, and its effects on disease parameters are assessed. For cardiovascular studies, blood pressure, endothelial function, and markers of oxidative stress are measured. For antiviral studies, viral load and immune responses are evaluated. The specific experimental design depends on the research question being addressed. The compound is typically administered orally, intraperitoneally, or intravenously.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of PD-404182 have been characterized to support its use as a research tool. The compound has a molecular weight of 217.29 and a molecular formula of C11H11N3S. It is soluble in DMF (30 mg/mL), DMSO (25 mg/mL), and ethanol (20 mg/mL), but has low solubility in aqueous buffers (0.09 mg/mL in DMF:PBS 1:10). The powder is stable when stored at -20°C. Specific PK parameters, such as half-life and bioavailability, are determined in animal studies via LC-MS/MS analysis of plasma samples. The compound's physicochemical properties suggest it has moderate lipophilicity and may have reasonable oral bioavailability.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for PD-404182 indicate that it exhibits minimal toxicity in vitro at concentrations up to 300 μM in various human cell lines, primary CD4+ T lymphocytes, macrophages, dendritic cells, and lactobacilli. It does not induce significant cytotoxicity in human dermal microvascular endothelial cells at concentrations of 10-300 μM over 24 hours. This favorable in vitro toxicological profile supports its use as a research tool. However, its safety profile in vivo requires further evaluation in animal models.
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| References |
[1]. Ghebremariam YT, et, al. A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a modulator of cardiovascular nitric oxide. J Pharmacol Exp Ther. 2014 Jan; 348(1): 69-76.
[2]. Chamoun-Emanuelli AM, et, al. Evaluation of PD 404,182 as an anti-HIV and anti-herpes simplex virus microbicide. Antimicrob Agents Chemother. 2014; 58(2): 687-97. |
| Additional Infomation |
Other information: PD-404182 is a research compound used to study the role of DDAH1 and ADMA in cardiovascular diseases, as well as its antiviral and antiangiogenic properties. It is also known as PD 404182 or PD404182. The compound is available from chemical suppliers for preclinical research purposes. Its CAS number is 72596-74-8.
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| Molecular Formula |
C11H11N3S
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| Molecular Weight |
217.29
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| Exact Mass |
217.067
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| CAS # |
72596-74-8
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| PubChem CID |
6603967
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.022
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
15
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| Complexity |
313
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C3=NCCCN3C(=N)S2
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| InChi Key |
JNENSSREQFBZGT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H11N3S/c12-11-14-7-3-6-13-10(14)8-4-1-2-5-9(8)15-11/h1-2,4-5,12H,3,6-7H2
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| Chemical Name |
3,4-dihydro-2H,6H-benzo[e]pyrimido[1,2-c][1,3]thiazin-6-imine
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| Synonyms |
PD404182 PD 404182 PD-404182
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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 (~230.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.51 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 (11.51 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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: ≥ 2.5 mg/mL (11.51 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 | 4.6021 mL | 23.0107 mL | 46.0214 mL | |
| 5 mM | 0.9204 mL | 4.6021 mL | 9.2043 mL | |
| 10 mM | 0.4602 mL | 2.3011 mL | 4.6021 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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