| Size | Price | Stock | Qty |
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| Targets |
PAR4
tcY-NH2 specifically targets the Protease-Activated Receptor 4 (PAR4), a GPCR primarily expressed on human platelets. It acts as a selective peptide antagonist. By blocking PAR4, tcY-NH2 prevents its activation by thrombin, a key protease in the coagulation cascade, thus modulating platelet activity. |
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| ln Vitro |
With an IC50 value of 95 μM, tcY-NH2 TFA (0-500 μM) inhibits the aggregation of platelets (obtained from male albino Sprague-Dawley rats) induced by AYPGKF-NH2 (10 μM). With IC50 values of 64 μM for aorta relaxation (RA) and 1 μM for gastric contraction (LM), tcY-NH2 TFA potently activates these processes[1]. tcY-NH2 TFA (Tc-YPGKF-NH2, 400 μM, 5 min) inhibits platelet aggregation and endostatin release that are brought on by thrombin or AY-NH2[2]. In an isolated heart model, tcY-NH2 TFA (5 μM, 15 min) increases recovery of ventricular function by 26% and decreases infarct size (IS) by 51%[5].
In vitro, tcY-NH2 TFA inhibits thrombin- and AY-NH2-induced platelet aggregation and endostatin release. It exhibits an IC50 value of 95 microM for general activity. In functional tissue assays, it potently activates aorta relaxation and gastric contraction, with IC50 values of 64 microM (relaxation) and 1 microM (contraction), respectively, showing potent bioactivity. |
| ln Vivo |
In the Brain Death (BD) rat model, tcY-NH2 TFA (tail vein injection, 0.6 mg/kg for a single dosage) reduces liver injury as seen by improved histomorphology and decreased blood ALT/AST levels[3]. In the draining lymph nodes of burn damage mice model, tcY-NH2 TFA (intraperitoneal injection, 0.6 mg/kg for a single dosage) promotes posttraumatic activation of CD4+ Tregs[4]. In experimental inflammation in mice, tcY-NH2 TFA (intrapleural injection, 40 ng/kg for a single dose) suppresses neutrophil recruitment[6].
In vivo activity data for tcY-NH2 TFA has not been published in standard chemical databases. Based on its in vitro mechanism (PAR4 antagonism), it is hypothesized to inhibit thrombosis in vivo. By blocking platelet aggregation, it could prolong bleeding time and prevent occlusive thrombus formation without affecting coagulation time. |
| Enzyme Assay |
tcY-NH2 TFA (Tc-YPGKF-NH2, 400 uM) could be used in receptor binding assays. However, specific radioligand binding protocols are not standard for peptide antagonists. A common method involves using a fluorescent-labeled PAR4 agonist and measuring fluorescence polarization when bound to PAR4-expressing membranes. The antagonist (tcY-NH2) is added to compete with the fluorescent ligand to determine Ki.
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| Cell Assay |
The standard assay for tcY-NH2 is platelet aggregation. Human platelet-rich plasma (PRP) is prepared from fresh blood via centrifugation (200g for 15 minutes). The PRP is pre-incubated with varying concentrations of tcY-NH2 TFA (10-400 uM) for 5 minutes. Thrombin (0.1 U/mL) or the PAR4-specific agonist AY-NH2 (100 uM) is added to induce aggregation. Aggregation is measured using an aggregometer, which tracks the increase in light transmission through the sample. The IC50 for inhibition of aggregation is calculated.
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| Animal Protocol |
Animal/Disease Models: Brain death (BD) rat model[3]
Doses: 0.6 mg/kg for a single dose Route of Administration: Tail vein injection for a single dose Experimental Results: decreased blood platelet activation and hepatic platelet accumulation. Attenuated the inflammatory response and apoptosis in the livers. Inhibited the activation of NF-κB and MAPK pathways induced by Brain death (BD). Animal/Disease Models: Burn injury model of C57BL/6 N mice[4] Doses: 0.6 mg/kg for a single dose Route of Administration: intraperitoneal (ip) injection Experimental Results: Increased expression and phosphorylation of PKC-θ in the presence of platelets, without affecting early posttraumatic hemostasis. Animal/Disease Models: BALB/c mice[6] Doses: 40 ng/kg for a single dose Route of Administration: Intrapleural injection Experimental Results: Abolished the number of rolling and adhering neutrophils on the vessel wall. Inhibited CXCL8- and Cg-induced neutrophil migration into the pleural cavity of mice. There are no standard published in vivo protocols for this peptide. A potential protocol would involve a ferric chloride-induced arterial thrombosis model in mice. tcY-NH2 is administered via intravenous injection (tail vein) at doses of 1-30 mg/kg. The carotid artery is injured with a FeCl3-soaked filter paper. Time to occlusion is monitored using a Doppler flow probe. A significantly longer time to occlusion compared to vehicle control indicates antithrombotic efficacy. |
| ADME/Pharmacokinetics |
tcY-NH2 TFA is a peptide antagonist; therefore, it is expected to have very poor oral bioavailability and a very short plasma half-life (minutes) due to extensive proteolytic degradation by peptidases in the blood and liver. It is typically administered intravenously or used in ex vivo assays. The TFA salt is used to improve solubility and stability in storage.
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| Toxicity/Toxicokinetics |
Specific toxicological data for tcY-NH2 TFA is not available. As a research peptide, its safety profile is not established. Peptide antagonists generally have low off-target toxicity. Since it targets platelet PAR4, high doses may increase the risk of bleeding. Standard safety studies would involve measuring bleeding time in animals and evaluating liver and kidney function markers after high-dose administration.
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| References |
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| Additional Infomation |
This compound is exclusively a research chemical and is not approved for clinical use. It is a valuable tool for investigating the specific role of the PAR4 receptor in platelet function, distinguishing it from PAR1 which is another thrombin receptor on human platelets. Because PAR4 is a promising target for new antiplatelet drugs that do not increase bleeding risk as much as current therapies, tcY-NH2 serves as a lead compound for drug discovery. The "TFA" in the name indicates the presence of trifluoroacetate counterions, common in peptide manufacturing.
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| Molecular Formula |
C42H50F3N7O9
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|---|---|
| Molecular Weight |
853.88
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| Exact Mass |
853.362
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| CAS # |
1262750-73-1
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| Related CAS # |
tcY-NH2;327177-34-4
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| PubChem CID |
71311594
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
61
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| Complexity |
1360
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1CN(C([C@@H](NC(/C=C/C2C=CC=CC=2)=O)CC2C=CC(O)=CC=2)=O)[C@H](C(NCC(N[C@H](C(N[C@H](C(N)=O)CC2C=CC=CC=2)=O)CCCCN)=O)=O)C1.O=C(C(F)(F)F)O
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| InChi Key |
WQJKBSZTPQERHW-USBDLMLUSA-N
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| InChi Code |
InChI=1S/C40H49N7O7.C2HF3O2/c41-22-8-7-14-31(38(52)46-32(37(42)51)24-28-12-5-2-6-13-28)44-36(50)26-43-39(53)34-15-9-23-47(34)40(54)33(25-29-16-19-30(48)20-17-29)45-35(49)21-18-27-10-3-1-4-11-27;3-2(4,5)1(6)7/h1-6,10-13,16-21,31-34,48H,7-9,14-15,22-26,41H2,(H2,42,51)(H,43,53)(H,44,50)(H,45,49)(H,46,52);(H,6,7)/b21-18+;/t31-,32-,33-,34-;/m0./s1
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| Chemical Name |
(2S)-N-[2-[[(2S)-6-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]-1-[(2S)-3-(4-hydroxyphenyl)-2-[[(E)-3-phenylprop-2-enoyl]amino]propanoyl]pyrrolidine-2-carboxamide;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: 100 mg/mL (117.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.44 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 (2.44 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 (2.44 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 | 1.1711 mL | 5.8556 mL | 11.7112 mL | |
| 5 mM | 0.2342 mL | 1.1711 mL | 2.3422 mL | |
| 10 mM | 0.1171 mL | 0.5856 mL | 1.1711 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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