| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of PPACK II diTFA is kallikrein, specifically both glandular and plasma kallikreins. It functions as an irreversible inhibitor by covalently binding to the active site of these serine proteases. It is also known to be a selective inhibitor for thrombin (with a Ki of 0.24 nM), and its inhibitory potency against Factor Xa is significantly lower (Ki ~240 nM).
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|---|---|
| ln Vitro |
B-type natriuretic peptide (BNP) proteolysis is greatly inhibited by PPACK II (0.62-50 μg/mL) diTFA [2].
The specificity of PPACK II (the active component) for thrombin is remarkable. Its inhibitory potency against Factor Xa is three orders of magnitude less, and its cross-reactivity with other coagulation factors is minimal. While not the parent compound, PPACK (without the TFA salt) is a benchmark for studying the coagulation cascade due to its high-affinity, irreversible binding to the active site of thrombin. |
| ln Vivo |
PPACK II diTFA has demonstrated in vitro activity by significantly inhibiting the proteolysis of B-type natriuretic peptide (BNP) at concentrations ranging from 0.62 to 50 microg/mL. This confirms the functional inhibition of its target proteases in a biochemical context, preventing the breakdown of a peptide substrate. Detailed in vivo activity studies for this specific salt form are not widely published.
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| Enzyme Assay |
A standard in vitro assay for the parent molecule, PPACK, involves measuring its inhibition constant (Ki) against purified thrombin. A typical protocol uses a chromogenic substrate for thrombin. PPACK is pre-incubated with thrombin in a reaction buffer to allow for irreversible binding. The substrate is then added, and the residual thrombin activity is measured by monitoring the release of p-nitroaniline at 405 nm over time. Ki values are calculated from reaction rates.
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| Cell Assay |
Cell-based assays are not the primary method for studying PPACK's mechanism, as it directly inhibits purified enzymes. However, to study its effect in a more complex environment, assays can be performed using cell lysates containing the target proteases. The compound is dissolved in DMSO and added to the cell lysate. The mixture is then incubated, and the activity of the target enzyme is measured using a fluorogenic or chromogenic substrate.
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| Animal Protocol |
In vivo studies for PPACK typically involve animal models of thrombosis. A common protocol is the ferric chloride-induced carotid artery injury model in mice. PPACK is administered via intravenous injection at a predetermined dose, and the time to occlusion of the blood vessel is measured to assess its antithrombotic efficacy. A vehicle control group is always included for comparison.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for PPACK II diTFA is not standardly available, as it is primarily a research biochemical tool. Given its peptide nature and the TFA counterion, its absorption, distribution, metabolism, and excretion profile would be complex. It is typically administered via injection in in vivo experiments to ensure systemic availability.
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| Toxicity/Toxicokinetics |
Detailed toxicological information for this specific compound is limited. As a research chemical for in vitro and controlled in vivo use, it is not intended for human consumption. Standard safety guidelines should be followed. For the parent molecule, high doses have been used in animal models without reports of systemic toxicity, but this does not constitute a comprehensive safety profile.
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| References |
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| Additional Infomation |
PPACK II diTFA is a valuable tool in pharmacology for investigating the specific roles of kallikreins and thrombin in physiological and pathological processes. Its irreversible mechanism of action distinguishes it from reversible inhibitors, allowing for stable and long-lasting inhibition. This property is crucial for experiments requiring sustained target blockade to study downstream signaling pathways.
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| Molecular Formula |
C29H35CLF6N6O7
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|---|---|
| Molecular Weight |
729.07
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| Exact Mass |
728.216
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| CAS # |
649748-23-2
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| Related CAS # |
PPACK II;74392-49-7
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| PubChem CID |
131698209
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
49
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| Complexity |
787
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C1=CC=C(C=C1)C[C@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)CCl)N.C(=O)(C(F)(F)F)O.C(=O)(C(F)(F)F)O
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| InChi Key |
JVMDQRDDGVKUMG-WOSURGFKSA-N
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| InChi Code |
InChI=1S/C25H33ClN6O3.2C2HF3O2/c26-16-22(33)20(12-7-13-30-25(28)29)31-24(35)21(15-18-10-5-2-6-11-18)32-23(34)19(27)14-17-8-3-1-4-9-17;2*3-2(4,5)1(6)7/h1-6,8-11,19-21H,7,12-16,27H2,(H,31,35)(H,32,34)(H4,28,29,30);2*(H,6,7)/t19-,20+,21+;;/m1../s1
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| Chemical Name |
(2R)-2-amino-N-[(2S)-1-[[(3S)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]-3-phenylpropanamide;2,2,2-trifluoroacetic acid
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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: 250 mg/mL (342.90 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.85 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 20.8 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: ≥ 2.08 mg/mL (2.85 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 20.8 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: ≥ 2.08 mg/mL (2.85 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 | 1.3716 mL | 6.8581 mL | 13.7161 mL | |
| 5 mM | 0.2743 mL | 1.3716 mL | 2.7432 mL | |
| 10 mM | 0.1372 mL | 0.6858 mL | 1.3716 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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