| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
The primary and specific target of DP-4088 is human thrombin (Factor IIa). Thrombin is a key serine protease in the blood coagulation cascade. It is generated from its inactive precursor, prothrombin, by the action of Factor Xa. Once activated, thrombin performs multiple critical functions: it cleaves fibrinogen into fibrin monomers, which polymerize to form a fibrin clot; it activates Factor XIII, which cross-links and stabilizes the clot; and it activates platelets via protease-activated receptors (PARs). By binding reversibly to the active site of thrombin, DP-4088 inhibits its catalytic activity, thereby blocking all of its downstream pro-coagulant functions. This direct and selective inhibition of thrombin makes DP-4088 a potent anticoagulant.
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| ln Vitro |
DP-4088 is a highly potent inhibitor of thrombin, with an IC₅₀ of 2.3 nM as determined in enzymatic assays. This high level of potency indicates that it is an extremely effective inhibitor at very low concentrations. Its mode of action is reversible, meaning that the inhibitor binds to the enzyme's active site in a non-covalent manner and can dissociate, allowing the enzyme to regain its activity. This reversibility is a key pharmacological feature that can offer advantages in terms of safety and manageability compared to irreversible anticoagulants. In vitro studies confirm its ability to inhibit thrombin activity and prevent fibrin clot formation in plasma. Its high selectivity for thrombin over other related serine proteases is a critical aspect of its profile as a potential therapeutic agent.
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| ln Vivo |
While DP-4088 has demonstrated potent in vitro activity, comprehensive in vivo data is not widely available in the public domain. However, its advancement into Phase I clinical development indicates that it was successfully evaluated in preclinical models and was deemed suitable for human testing. In vivo, a direct thrombin inhibitor like DP-4088 is expected to effectively prolong clotting times, such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT), and prevent thrombus formation in animal models of thrombosis. Its oral bioavailability would be a key factor in its in vivo efficacy, enabling convenient once-daily dosing.
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| Enzyme Assay |
The in vitro enzyme assay for DP-4088 typically measures its ability to inhibit the catalytic activity of human thrombin. In this assay, purified human thrombin is incubated with a specific chromogenic or fluorogenic substrate that mimics its natural substrate, fibrinogen. Cleavage of the substrate by thrombin releases a detectable signal (color or fluorescence). The assay is performed in the presence of varying concentrations of DP-4088. The enzyme activity is measured by monitoring the rate of signal generation. A control without the inhibitor defines 100% enzyme activity. By plotting the percent inhibition versus the compound concentration, an IC₅₀ value can be calculated, which for DP-4088 is 2.3 nM. This assay is a standard and robust method for characterizing direct thrombin inhibitors.
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| Cell Assay |
In vitro cell-based assays for DP-4088 typically evaluate its anticoagulant effects in a more complex biological context, such as in human plasma or whole blood. The compound is added to platelet-poor plasma, and clotting is initiated by the addition of a trigger, such as tissue factor or a contact activator. The time to clot formation is measured using a coagulometer. The compound's ability to prolong the clotting time in a concentration-dependent manner is a direct measure of its anticoagulant activity. These assays, such as the aPTT and PT assays, are used to translate the biochemical enzyme inhibition into a functional anticoagulant effect.
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| Animal Protocol |
In vivo animal studies for DP-4088 would have been conducted to support its development as an anticoagulant. Standard models include rodent models of thrombosis, such as the ferric chloride-induced arterial thrombosis model or the venous stasis model. In these models, thrombosis is induced in a blood vessel, and the effect of the compound on thrombus formation is assessed. DP-4088 would typically be administered orally to evaluate its ability to prevent or reduce clot formation. These studies are crucial for demonstrating in vivo efficacy and for establishing the dose-response relationship.
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| ADME/Pharmacokinetics |
DP-4088 was specifically engineered for once-daily oral dosing. This suggests that it possesses favorable pharmacokinetic properties, including good oral bioavailability and a sufficiently long half-life to maintain therapeutic concentrations throughout the day. The compound was advanced into Phase I clinical development, meaning that human pharmacokinetic and pharmacodynamic (PK/PD) data were generated. However, detailed PK parameters are not typically published for compounds that are not ultimately approved. Its chemical properties, including a molecular weight of 452.8, suggest it has drug-like characteristics suitable for oral administration.
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| Toxicity/Toxicokinetics |
As a compound that entered clinical development, DP-4088 would have undergone extensive preclinical toxicology studies to assess its safety. However, specific toxicity data is not publicly available. The primary safety concern with any anticoagulant is the risk of bleeding. Therefore, the therapeutic window of DP-4088 would have been carefully evaluated in toxicology studies to balance efficacy (preventing clots) with safety (avoiding excessive bleeding). As a reversible inhibitor, it may have a more manageable safety profile than irreversible anticoagulants like warfarin.
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| References | |
| Additional Infomation |
DP-4088 (Thrombin Inhibitor 2) is a significant compound in the history of anticoagulant drug development. It represents a class of direct, reversible thrombin inhibitors that were explored as oral alternatives to warfarin. The compound was advanced into Phase I clinical development for the prevention of venous thromboembolism. However, it appears that development was discontinued, as it did not progress to later-stage trials or receive FDA approval. It is now available as a high-purity research reagent for studying coagulation pathways and for use as a reference standard in enzymatic assays.
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| Molecular Formula |
C19H16CLF3N6O2
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| Molecular Weight |
452.8222
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| Exact Mass |
452.098
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| CAS # |
312904-62-4
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| PubChem CID |
9955534
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| Appearance |
White to off-white solid powder
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| LogP |
2.608
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
735
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AATHXZYXWMKUFC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16ClF3N6O2/c20-15-9-27-17(28-11-19(22,23)14-5-1-2-6-25-14)18(31)29(15)10-16(30)26-8-13-12(21)4-3-7-24-13/h1-7,9H,8,10-11H2,(H,26,30)(H,27,28)
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| Chemical Name |
2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]-N-[(3-fluoropyridin-2-yl)methyl]acetamide
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| Synonyms |
DP4088; DP 4088; DP-4088
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~110.42 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 | 2.2084 mL | 11.0419 mL | 22.0838 mL | |
| 5 mM | 0.4417 mL | 2.2084 mL | 4.4168 mL | |
| 10 mM | 0.2208 mL | 1.1042 mL | 2.2084 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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