| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
Cyclo(his-pro) TFA inhibits NF-κB nuclear accumulation while promoting Nrf2 activation. It targets the NF-κB and Nrf2 signaling pathways, key regulators of inflammation and oxidative stress. By modulating these pathways, it attenuates inflammatory and stress responses. The compound's ability to cross the blood-brain barrier makes it particularly valuable for studying neuroinflammation and central nervous system stress responses. It does not have a single classical receptor target but acts through pathway modulation.
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| ln Vitro |
The 50 μM solution of Cyclo(his-pro) TFA (Cyclo(histidyl-proline) TFA; 1-48 hours) raises nuclear Nrf2 levels and prevents NF-κB nuclear translocation. These transcription factors' nuclear translocation is unaffected by cyclo(His-Pro) alone [2]. After exposure to paraquat (PQ), cyclo(his-pro) TFA (50 μM; 48 h prior to PQ exposure) removes protein nitration and reduces its functional effects, including cytochrome c release and caspase 3 activity [2]. Through the Nrf2/hemeoxygenase-1 pathway, cyclo(his-pro) TFA prevents NF-κB from building up nuclear in rat pheochromocytoma PC12 cells when paraquat is applied [2].
In vitro, Cyclo(his-pro) TFA (50 μM; 1-48 hours) increases the nuclear level of Nrf2 and inhibits NF-κB nuclear translocation. It abolishes protein nitration that follows paraquat (PQ) exposure and lessens its functional consequences, as shown by a decrease in cell apoptosis, detected by caspase 3 activity and by cytochrome c release. In rat pheochromocytoma PC12 cells, it inhibits NF-κB nuclear accumulation induced by paraquat via the Nrf2/heme oxygenase-1 pathway. |
| ln Vivo |
Cyclo(his-pro) TFA (Cyclo(his-pro) TFA; 1.8 mg/ear; applied topically to the right ear; 30 minutes before TPA) can reduce TPA-induced ear edema, confirming that it can exert an anti-inflammatory effect [ 2 ]. Cyclo(his-pro) TFA exerts in vivo anti-inflammatory effects in the central nervous system by downregulating TNFα expression in liver and brain, thereby counteracting LPS-induced gliosis. In addition, Cyclo (his-pro) relieves ER stress by upregulating Bip, increasing ER stress sensitivity and triggering the unfolded protein response [3].
In vivo, Cyclo(his-pro) TFA exerts anti-inflammatory effects in the central nervous system by down-regulating hepatic and cerebral TNFα expression, thereby counteracting LPS-induced gliosis. Topical application of 1.8 mg/ear 30 minutes prior to TPA reduces TPA-induced ear edema, confirming its anti-inflammatory effect. By up-regulating Bip, it increases ER stress sensitivity and triggers the unfolded protein response to alleviate ER stress. |
| Enzyme Assay |
Cell-free assays for Cyclo(his-pro) TFA typically involve studying its effects on NF-κB and Nrf2 pathways using purified proteins or nuclear extracts. NF-κB DNA binding activity can be assessed using electrophoretic mobility shift assays (EMSA) or ELISA-based kits. Nrf2 activation can be measured by its translocation and binding to antioxidant response elements (ARE) in cell-free systems. The compound's chemical purity and identity are confirmed by HPLC, NMR, and mass spectrometry. It is typically dissolved in DMSO or appropriate buffers for assay preparation.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: PC12 cells Tested Concentrations: 50 μM Incubation Duration: 1, 2, 4, 8, 24, 48 hrs (hours) Experimental Results: Nrf2 nuclear levels increased and NF-κB nuclear translocation was inhibited. In vitro cellular assays for Cyclo(his-pro) TFA typically involve treating PC12 cells or other neuronal cell lines with the compound at 50 μM for 1-48 hours. NF-κB nuclear translocation is assessed by western blotting of nuclear and cytoplasmic fractions or by immunofluorescence microscopy. Nrf2 nuclear levels are measured similarly. Oxidative stress markers such as protein nitration are evaluated. Apoptosis is detected by caspase 3 activity assays and cytochrome c release measurements. |
| Animal Protocol |
Animal/Disease Models: Sixty-two/three-month-old male C57BL/6 mice (25-30 g) [2]
Doses: 1.8 mg/ear Route of Administration: Apply topically to the right ear; 30 minutes before TPA Experimental Results:TPA Reduce ear edema caused. In vivo animal studies for Cyclo(his-pro) TFA are conducted in mouse models. For anti-inflammatory assessment, TPA-induced ear edema models are used, with the compound applied topically at 1.8 mg/ear 30 minutes prior to TPA. For central nervous system effects, LPS-induced gliosis models are employed, and TNFα expression in liver and brain is measured. C57BL/6 mice (25-30 g) are commonly used. ER stress is evaluated by measuring Bip upregulation and unfolded protein response markers. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Cyclo(his-pro) TFA include a molecular weight of 348.28 g/mol, molecular formula C13H15F3N4O4, and purity ≥95%. It is orally active and can cross the blood-brain barrier. The compound is typically stored as a powder at -20°C for up to 3 years and in solvent at -80°C for 1 year. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of Cyclo(his-pro) TFA has not been extensively characterized in published literature. As a cyclic dipeptide that modulates NF-κB and Nrf2 pathways, it is generally well-tolerated at research doses. Standard preclinical safety studies would include acute and sub-chronic toxicity assessments in rodent models. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Cyclo(his-pro) TFA is an orally active cyclic dipeptide structurally related to TRH that crosses the BBB. It inhibits NF-κB nuclear accumulation while promoting Nrf2 activation, attenuating oxidative stress and inflammatory signaling. In vitro, 50 μM Cyclo(his-pro) TFA increases nuclear Nrf2 and inhibits NF-κB translocation. In vivo, it reduces TPA-induced ear edema (1.8 mg/ear) and counteracts LPS-induced gliosis by downregulating TNFα. It is a research tool for neuroinflammation and oxidative stress studies, not for therapeutic use.
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| Molecular Formula |
C13H15F3N4O4
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|---|---|
| Molecular Weight |
348.277813196182
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| Exact Mass |
348.104
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| CAS # |
936749-56-3
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| Related CAS # |
Cyclo(his-pro);53109-32-3
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| PubChem CID |
145925626
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
430
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(F)(F)(F)C(=O)O.O=C1[C@H](CC2NC=NC=2)NC(=O)[C@@H]2CCCN12
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| InChi Key |
YOFCDSUBRJNLBB-OZZZDHQUSA-N
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| InChi Code |
InChI=1S/C11H14N4O2.C2HF3O2/c16-10-9-2-1-3-15(9)11(17)8(14-10)4-7-5-12-6-13-7;3-2(4,5)1(6)7/h5-6,8-9H,1-4H2,(H,12,13)(H,14,16);(H,6,7)/t8-,9-;/m0./s1
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| Chemical Name |
(3S,8aS)-3-(1H-imidazol-5-ylmethyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione;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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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 : ~260 mg/mL (~746.53 mM)
H2O : ~125 mg/mL (~358.91 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (6.23 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 21.7 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: ≥ 2.17 mg/mL (6.23 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 21.7 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: ≥ 2.17 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (287.13 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8713 mL | 14.3563 mL | 28.7125 mL | |
| 5 mM | 0.5743 mL | 2.8713 mL | 5.7425 mL | |
| 10 mM | 0.2871 mL | 1.4356 mL | 2.8713 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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