| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
TD-0212 TFA targets the angiotensin II type 1 receptor (AT1) as an antagonist with a pKi of 8.9, and neprilysin (NEP) as an inhibitor with a pIC50 of 9.2. By combining AT1 blockade with NEP inhibition, TD-0212 enhances antihypertensive efficacy while potentially lowering the risk of angioedema compared with dual ACE/NEP inhibition.
|
|---|---|
| ln Vitro |
TD-0212 increases the activity of dual AT1/NEP inhibition in comparison to dual ACE/NEP inhibition, and it may also lower the risk of angioedema [1].
In vitro, TD-0212 TFA is characterized as a potent AT1 antagonist and NEP inhibitor. It shows dual pharmacology with high potency at both targets. The compound's activity at AT1 and NEP makes it a valuable tool for studying the renin-angiotensin system and the role of natriuretic peptides in cardiovascular physiology. |
| ln Vivo |
In renin-dependent and -independent hypertension models, TD-0212 lowers blood pressure in a manner akin to that of omapatrilat and the combination of AT1 receptor antagonists and NEP inhibitors [1].
In vivo, TD-0212 produces blood pressure reductions similar to omapatrilat and to combinations of AT1 receptor antagonists with NEP inhibitors. In preclinical hypertension models, TD-0212 demonstrates antihypertensive efficacy. Its dual mechanism provides enhanced activity with a potentially lower risk of angioedema relative to dual ACE/NEP inhibition. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for TD-0212 TFA involve measuring its affinity for the AT1 receptor and its inhibition of NEP. Radioligand binding studies using ³H-angiotensin II or other AT1 ligands are performed on membranes expressing the receptor. NEP activity is measured using a fluorogenic substrate (e.g., dansyl-D-Ala-Gly-p-nitro-Phe-Gly). IC50 and Ki values are calculated from dose-response curves.
|
| Cell Assay |
For in vitro cell-based assays, cells expressing the AT1 receptor are cultured and treated with TD-0212 TFA. Receptor antagonism is confirmed by its ability to block angiotensin II-induced signaling, such as calcium mobilization or ERK phosphorylation. NEP inhibition can be assessed by measuring the degradation of natriuretic peptides in cell culture supernatants. Cell viability is assessed by MTT or standard assays.
|
| Animal Protocol |
In vivo animal studies with TD-0212 TFA are conducted in models of hypertension. The compound is administered orally to hypertensive rats. Blood pressure is measured by telemetry or tail-cuff. The compound's effects on blood pressure, heart rate, and other hemodynamic parameters are monitored. Its efficacy is compared to other antihypertensive agents such as omapatrilat.
|
| ADME/Pharmacokinetics |
TD-0212 TFA (CAS: 1073549-11-7) has a molecular weight of 641.67 g/mol and a molecular formula of C30H35F4N3O6S. Synonyms: TD-0212 trifluoroacetate. Purity: ≥95%. Solubility: DMSO. Storage: powder at -20°C. The compound is an orally active dual AT1 antagonist and NEP inhibitor.
|
| Toxicity/Toxicokinetics |
TD-0212 TFA is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a dual AT1/NEP inhibitor, it may have effects on blood pressure and fluid balance. The compound's design aims to lower the risk of angioedema compared to ACE/NEP inhibitors. Standard laboratory safety precautions should be followed.
|
| References | |
| Additional Infomation |
TD-0212 TFA is an orally active dual-acting small molecule that functions as both an AT1 antagonist (pKi = 8.9) and a NEP inhibitor (pIC50 = 9.2). It enhances antihypertensive efficacy while potentially lowering the risk of angioedema compared with dual ACE/NEP inhibition. It is a valuable research tool for cardiovascular disease research. It is not FDA-approved and is intended for research use only.
|
| Molecular Formula |
C30H35F4N3O6S
|
|---|---|
| Molecular Weight |
641.67402100563
|
| Exact Mass |
641.218
|
| CAS # |
1073549-11-7
|
| Related CAS # |
TD-0212;1073549-10-6
|
| PubChem CID |
145925648
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
44
|
| Complexity |
828
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S[C@H](C(NCC1=C(CC)N=C(N1CC1C=CC(C2C=CC=CC=2C(=O)O)=CC=1F)OCC)=O)CC(C)C.FC(C(=O)O)(F)F
|
| InChi Key |
HYFVVNVEHLLCLR-UQIIZPHYSA-N
|
| InChi Code |
InChI=1S/C28H34FN3O4S.C2HF3O2/c1-5-23-24(15-30-26(33)25(37)13-17(3)4)32(28(31-23)36-6-2)16-19-12-11-18(14-22(19)29)20-9-7-8-10-21(20)27(34)35;3-2(4,5)1(6)7/h7-12,14,17,25,37H,5-6,13,15-16H2,1-4H3,(H,30,33)(H,34,35);(H,6,7)/t25-;/m0./s1
|
| Chemical Name |
2-[4-[[2-ethoxy-4-ethyl-5-[[[(2S)-4-methyl-2-sulfanylpentanoyl]amino]methyl]imidazol-1-yl]methyl]-3-fluorophenyl]benzoic acid;2,2,2-trifluoroacetic acid
|
| Synonyms |
TD0212 TFA; TD 0212 TFA
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~194.80 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.24 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 (3.24 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 (3.24 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 | 1.5584 mL | 7.7922 mL | 15.5843 mL | |
| 5 mM | 0.3117 mL | 1.5584 mL | 3.1169 mL | |
| 10 mM | 0.1558 mL | 0.7792 mL | 1.5584 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
