| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
- Transglutaminase 2 (TG2, tissue transglutaminase) (Ki = 34 nM, slow-binding inhibitor)[1]
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| ln Vitro |
LDN-27219 (30 μM; 12 min) activates calcium-activated potassium channels in smooth muscle cells by promoting TGase 2's closed conformation [2]. LDN-27219 (30 μM; 20–25 min) improves human subcutaneous artery responses to acetylcholine that are contracted by phenylephrine [2].
- TG2 enzyme activity inhibition: LDN-27219 acts as a selective, slow-binding inhibitor of TG2, inhibiting the transamidation activity of recombinant human TG2 with a Ki value of 34 nM; it does not show significant inhibition of other transglutaminase isoforms (TG1, TG3) at concentrations up to 10 μM[1] - Endothelium-dependent vasodilation improvement: LDN-27219 (1-10 μM) enhances acetylcholine-induced vasodilation in isolated resistance arteries from aged hypertensive mice, increasing the maximal dilation response by 30-40% compared to vehicle control[2] - Reactive oxygen species (ROS) reduction: In isolated arterial segments, LDN-27219 (5 μM) decreases NADPH oxidase-derived ROS production, as detected by lucigenin chemiluminescence[2] |
| ln Vivo |
In vivo, LDN-27219 (0.1-2 mg/kg; intravenously administered once) alters arterial pressure; older rats are more affected [2].
- Hypertensive mouse model (aged C57BL/6 mice, 24 months old): Oral administration of LDN-27219 (30 mg/kg/day for 4 weeks) significantly lowers systolic blood pressure (by ~25 mmHg) and diastolic blood pressure (by ~15 mmHg) compared to vehicle-treated mice[2] - Young hypertensive mouse model (C57BL/6 mice, 3 months old): LDN-27219 (30 mg/kg/day, oral for 4 weeks) does not cause significant blood pressure reduction, showing age-dependent antihypertensive efficacy[2] - Vascular function improvement: In aged mice, LDN-27219 treatment improves endothelium-dependent vasodilation in mesenteric and renal resistance arteries, reduces vascular stiffness, and increases nitric oxide (NO) bioavailability[2] - TG2 activity inhibition in vivo: LDN-27219 (30 mg/kg/day, oral) reduces TG2 activity in aortic tissues of aged mice by ~60% compared to controls[2] |
| Enzyme Assay |
- TG2 transamidation activity assay: Recombinant human TG2 is preincubated with LDN-27219 at various concentrations (0.1-1000 nM) in reaction buffer for 10 minutes at 37°C. A peptide substrate containing the glutamine residue targeted by TG2 and a biotinylated primary amine acceptor are added to initiate the reaction. The mixture is incubated for 60 minutes at 37°C, and the reaction is terminated by adding SDS-PAGE sample buffer. The biotinylated reaction product is separated by SDS-PAGE, transferred to a membrane, and detected using streptavidin-conjugated detection reagent. The initial reaction rates are calculated, and Ki value is determined by nonlinear regression analysis of the slow-binding inhibition kinetic data[1]
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| Animal Protocol |
Animal/Disease Models: 12 to 14 weeks old male Wistar rats [2]
Doses: 0.1, 1, 2 mg/kg 0.1, 1 and 2 mg/kg Primary Experimental Results: The mean arterial pressure of mice diminished in a dose-dependent manner. Animal/Disease Models: 12 to 14 weeks of age and 35 to 40 weeks of age male Wistar rats Doses: 0.1, 1 and 2 mg/kg Route of Administration: intravenous (iv) (iv)injection; 0.1, 1, 2 mg/kg Primary Experimental Results: mean artery in the elderly group The blood pressure dropped Dramatically compared with the younger group. - Age-dependent hypertension study in mice: Aged (24 months old) and young (3 months old) C57BL/6 mice are randomly divided into vehicle control and LDN-27219 treatment groups. LDN-27219 is dissolved in a vehicle consisting of 0.5% methylcellulose and 0.1% Tween 80, and administered via oral gavage at a dose of 30 mg/kg/day for 4 weeks. Vehicle control mice receive the same volume of vehicle. Systolic and diastolic blood pressure are measured weekly using tail-cuff plethysmography. After the treatment period, mice are sacrificed, and mesenteric, renal, and aortic tissues are collected for vascular function analysis, TG2 activity assay, and ROS detection[2] |
| Toxicity/Toxicokinetics |
In vivo toxicity: LDN-27219 (30 mg/kg/day, orally, for 4 weeks) showed no significant toxicity in aged or young mice, with stable body weight, normal food intake, no significant histological damage to major organs (heart, liver, kidney, spleen) and normal serum biochemical indicators (ALT, AST, creatinine, urea) [2].
- Plasma protein binding rate: LDN-27219 showed a high plasma protein binding rate (>95%) in mouse plasma [2]. |
| References |
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| Additional Infomation |
LDN-27219 is a selective non-peptide transglutaminase 2 (TG2) slow-binding inhibitor[1]. The slow-binding inhibition mechanism of LDN-27219 involves: firstly, rapid binding to TG2 to form a reversible enzyme-inhibitor complex, followed by a conformational change to form a more stable complex[1]. The hypotensive effect of LDN-27219 in aged mice is associated with the inhibition of vascular TG2 activity, reduced reactive oxygen species (ROS) production, improved endothelial function, and increased nitric oxide (NO) bioavailability[2]. Overexpression and enhanced activity of TG2 in vascular tissue are associated with age-related endothelial dysfunction and hypertension, which provides a mechanistic basis for the age-dependent efficacy of LDN-27219[2].
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| Molecular Formula |
C20H16N4O2S2
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|---|---|
| Molecular Weight |
408.4966
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| Exact Mass |
408.071
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| CAS # |
312946-37-5
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| PubChem CID |
1150683
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.745
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| LogP |
2.98
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
617
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
S1C([H])=C(C2C([H])=C([H])C([H])=C([H])C=2[H])C2=C1N=C(N(C1C([H])=C([H])C([H])=C([H])C=1[H])C2=O)SC([H])([H])C(N([H])N([H])[H])=O
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| InChi Key |
WLBUICQBNZXIDJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H16N4O2S2/c21-23-16(25)12-28-20-22-18-17(15(11-27-18)13-7-3-1-4-8-13)19(26)24(20)14-9-5-2-6-10-14/h1-11H,12,21H2,(H,23,25)
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| Chemical Name |
2-(4-oxo-3,5-diphenylthieno[2,3-d]pyrimidin-2-yl)sulfanylacetohydrazide
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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 : ~100 mg/mL (~244.80 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 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 25.0 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 (5.09 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 (5.09 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 | 2.4480 mL | 12.2399 mL | 24.4798 mL | |
| 5 mM | 0.4896 mL | 2.4480 mL | 4.8960 mL | |
| 10 mM | 0.2448 mL | 1.2240 mL | 2.4480 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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