| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
ZED-1227 targets transglutaminase 2 (TG2), also known as tissue transglutaminase (TGM2), which is the key enzyme responsible for gluten-induced intestinal damage in celiac disease. It is a specific and potent inhibitor of TG2 with an IC50 of 45 nM. By inhibiting TG2, ZED-1227 blocks inflammation-induced TG2 expression and activation.
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| ln Vitro |
ZED-1227 (0.1 μM-1 μM; 24 hours) does not affect Huh7 or CaCo2 cell proliferation or metabolic activities, indicating that ZED-1227 is not cytotoxic [2]. In vitro, ZED-1227 (0.002-0.2 mg/mL; 30 minutes) suppresses TG2 in the mucosa of the small intestine[2].
ZED-1227 is a potent inhibitor of transglutaminase 2 (TG2) with an IC50 of 45 nM. It blocks inflammation-induced TG2 expression and activation. The compound has anticancer activity. ZED-1227 is a specific and orally active TG2 inhibitor. |
| ln Vivo |
ZED-1227 can decrease intestinal inflammation in mice and bring the intestinal TG2 activity generated by Polyinosinic:Polycytidylic Acid (40 mg/kg) down to normal control levels [1]. ?Inhibiting TG2 in the small intestine mucosa is ZED-1227 (5 mg/kg; ig)[2].
Specific in vivo activity data for ZED-1227 are not extensively reported in the available literature. As a potent TG2 inhibitor, it is expected to exhibit efficacy in preclinical models of celiac disease. The compound can be used for the research of celiac disease (CeD). Further research is needed to characterize its pharmacokinetic and pharmacodynamic profiles in animal models. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for ZED-1227 typically involves measuring its inhibitory activity against transglutaminase 2 (TG2) using a standard enzyme assay. The compound is incubated with the enzyme and a substrate, and the transglutaminase activity is measured. The IC50 value is determined from the dose-response curve.
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| Cell Assay |
The in vitro cellular assay for ZED-1227 typically involves culturing cells that express TG2 in appropriate growth media. Cells are treated with varying concentrations of the compound, and TG2 activity or expression is measured. The compound's effects on inflammation-induced TG2 expression and activation are assessed.
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse [2]
Doses: 5 mg/kg Route of Administration: po (oral gavage) Experimental Results:Inhibition of TG2 in the small intestinal mucosa in vivo. In vivo animal studies for ZED-1227 would typically involve the use of mouse models of celiac disease or gluten sensitivity. Animals would be administered the compound via oral gavage at various doses, and intestinal damage, inflammatory markers, and TG2 activity would be assessed. The compound's efficacy in preventing gluten-induced intestinal damage would be evaluated. |
| ADME/Pharmacokinetics |
ZED-1227 has a molecular weight of 528.60 g/mol and a molecular formula of C26H36N6O6. The IUPAC name is (2E,6S)-7-[[1-[2-[(2-Ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1H-imidazol-5-yl)carbonyl]amino]-7-oxo-2-heptenoic Acid Methyl Ester. The compound has a purity of ≥98%. Further detailed physicochemical properties are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Specific toxicology data for ZED-1227 are not available in the public domain. The compound is intended for research use only and should be handled with appropriate laboratory safety precautions. Standard safety assessments would be required before any clinical application. Researchers should consult the safety data sheet for detailed handling and disposal information.
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| References | |
| Additional Infomation |
ZED-1227 (TAK-227) is a specific, orally active, and potent transglutaminase 2 (TG2) inhibitor with an IC50 of 45 nM. It blocks inflammation-induced TG2 expression and activation and can be used for the research of celiac disease (CeD). The compound has anticancer activity. It is a promising therapeutic agent for celiac disease. It has not yet entered clinical trials and is strictly for preclinical research purposes.
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| Molecular Formula |
C26H36N6O6
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|---|---|
| Molecular Weight |
528.600646018982
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| Exact Mass |
528.269
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| CAS # |
1542132-88-6
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| PubChem CID |
72950407
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
38
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| Complexity |
958
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(N(C)C=NC=1)C(=O)N[C@@H](CC/C=C/C(=O)OC)C(=O)NC1C(=O)N(CC(=O)NCC(CC)CC)C=CC=1
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| InChi Key |
VHGWUSABWIEXKQ-BEBFYNPSSA-N
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| InChi Code |
InChI=1S/C26H36N6O6/c1-5-18(6-2)14-28-22(33)16-32-13-9-11-20(26(32)37)30-24(35)19(10-7-8-12-23(34)38-4)29-25(36)21-15-27-17-31(21)3/h8-9,11-13,15,17-19H,5-7,10,14,16H2,1-4H3,(H,28,33)(H,29,36)(H,30,35)/b12-8+/t19-/m0/s1
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| Chemical Name |
methyl
(S,E)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl)amino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate
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| Synonyms |
ZED-1227 ZED 1227 ZED1227
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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 : ~125 mg/mL (~236.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (3.93 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (3.93 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 (3.93 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 | 1.8918 mL | 9.4589 mL | 18.9179 mL | |
| 5 mM | 0.3784 mL | 1.8918 mL | 3.7836 mL | |
| 10 mM | 0.1892 mL | 0.9459 mL | 1.8918 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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