| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
Temanogrel targets the 5-HT2A receptor, a G protein-coupled receptor that mediates vasoconstriction, platelet aggregation, and smooth muscle contraction. By antagonizing the 5-HT2A receptor, temanogrel inhibits serotonin-induced platelet aggregation and vasoconstriction. This mechanism has potential therapeutic applications in cardiovascular diseases and conditions involving excessive platelet activation.
|
|---|---|
| ln Vitro |
Temanogrel has a Ki of 4.9 nM and is an extremely selective antagonist of the 5-HT2A receptor. Temanogrel has an IC50 of 5.2 nM, which prevents the buildup of phosphoinositides. With IC50 values of 8.7 and 23.1 nM, respectively, temanogrel potently suppresses serotonin-mediated amplification of ADP-stimulated platelet aggregation in both humans and dogs [1]. Temanogrel pretreatment of aortic rings inhibited the concentration-dependent vasoconstriction elicited by 20 μM 5-HT. With an IC50 of 13±7 nM, Temanogrel preincubation likewise strongly suppresses 5-HT-stimulated DNA synthesis[3].
In vitro, temanogrel is a selective 5-HT2A receptor antagonist. Its activity is assessed using radioligand binding assays to determine receptor affinity and functional assays to measure antagonism of serotonin-induced responses. The compound's selectivity for 5-HT2A over other serotonin receptor subtypes and other receptor families is determined in receptor profiling studies. |
| ln Vivo |
Throughout the experiment, there were no changes in heart rate or mean arterial pressure between the groups receiving saline or Temanogrel (i.e., P between groups = 0.508 for mean arterial pressure, P for interaction between groups = 0.540). Temanogrel-treated dogs exhibited a swift and steady rise in plasma Temanogrel levels, with mean increases of 25.5±4.1, 28.7±4.6, and 31.2±4.5 ng/mL at 10 minutes, 1.25 hours, and 2.25 hours following the initiation of therapy, respectively. 3].
In vivo, temanogrel has been studied in animal models of thrombosis and vasospasm. By blocking 5-HT2A receptors, the compound inhibits serotonin-induced platelet aggregation and vasoconstriction, potentially reducing the risk of thrombotic events. Its effects on hemodynamic parameters and inflammatory markers have also been evaluated in preclinical studies. |
| Enzyme Assay |
In vitro receptor binding assays for temanogrel measure its affinity for the 5-HT2A receptor using radioligand displacement techniques. Membranes prepared from cells expressing the receptor are incubated with a radiolabeled 5-HT2A ligand and varying concentrations of the compound. The binding affinity (Ki) is calculated from competitive binding curves. Functional assays measure antagonism of serotonin-induced calcium mobilization or other signaling readouts.
|
| Cell Assay |
In vitro cell-based assays for temanogrel use cells expressing the 5-HT2A receptor. Cells are treated with serial dilutions of the compound, and serotonin-induced responses such as calcium mobilization, phospholipase C activation, or other downstream signaling events are measured. The IC50 for inhibition of serotonin responses is calculated from dose-response curves. Cell viability is assessed in parallel.
|
| Animal Protocol |
In vivo animal models for temanogrel include models of thrombosis, such as arterial or venous thrombosis models, and models of vasospasm. The compound is administered orally or intravenously, and its effects on thrombus formation, platelet aggregation, and vascular tone are evaluated. Pharmacodynamic studies measure 5-HT2A receptor occupancy and inhibition of serotonin-induced responses.
|
| ADME/Pharmacokinetics |
Temanogrel has a molecular formula and weight that are documented in research publications. The compound is orally bioavailable and is administered orally or intravenously in preclinical studies. It is soluble in DMSO and other organic solvents. Pharmacokinetic parameters including half-life, bioavailability, and tissue distribution are documented in research publications.
|
| Toxicity/Toxicokinetics |
The toxicity profile of temanogrel is characterized in preclinical safety studies. As a 5-HT2A receptor antagonist, the compound is generally well-tolerated at therapeutic doses. Common adverse effects may include gastrointestinal discomfort. The compound is for research use only and not for human use. Appropriate safety precautions should be taken during handling.
|
| References |
[1]. Xiong Y, et al. Discovery and structure-activity relationship of 3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide (APD791): a highly selective 5-hydroxytryptamine2A receptor inverse agonist for the treatment of arterial thr
[2]. Przyklenk K, et al. Targeted inhibition of the serotonin 5HT2A receptor improves coronary patency in an in vivo model of recurrent thrombosis. J Thromb Haemost. 2010 Feb;8(2):331-40. [3]. Adams JW, et al. APD791, 3-methoxy-n-(3-(1-methyl-1h-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide, a novel 5-hydroxytryptamine 2A receptor antagonist: pharmacological profile, pharmacokinetics, platelet activity and vascular biology. J Pharmacol E |
| Additional Infomation |
Temanogre belongs to the benzamide class of drugs.
See also: Temanogre (note moved to). Temanogrel is a selective 5-HT2A receptor antagonist with potential therapeutic applications in cardiovascular and inflammatory diseases. It has been investigated for the treatment of conditions involving platelet aggregation and vasoconstriction. The compound's mechanism involves antagonism of the 5-HT2A receptor, inhibiting serotonin-induced platelet aggregation and vasoconstriction. Temanogrel is used for research purposes only. |
| Molecular Formula |
C24H28N4O4
|
|---|---|
| Molecular Weight |
436.512
|
| Exact Mass |
436.211
|
| CAS # |
887936-68-7
|
| PubChem CID |
11604525
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.38
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
32
|
| Complexity |
588
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1C=C(OC)C=CC=1)NC1C=C(C2N(C)N=CC=2)C(OCCN2CCOCC2)=CC=1
|
| InChi Key |
ZEOQUKRCASTCFR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H28N4O4/c1-27-22(8-9-25-27)21-17-19(26-24(29)18-4-3-5-20(16-18)30-2)6-7-23(21)32-15-12-28-10-13-31-14-11-28/h3-9,16-17H,10-15H2,1-2H3,(H,26,29)
|
| Chemical Name |
3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4-ylethoxy)phenyl]benzamide
|
| Synonyms |
APD 791; APD-791; APD791
|
| 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 |
| 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 (~286.37 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.32 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 62.5 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: ≥ 6.25 mg/mL (14.32 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 62.5 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: ≥ 6.25 mg/mL (14.32 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 | 2.2909 mL | 11.4545 mL | 22.9090 mL | |
| 5 mM | 0.4582 mL | 2.2909 mL | 4.5818 mL | |
| 10 mM | 0.2291 mL | 1.1454 mL | 2.2909 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04915950
Conditions:Raynaud's Phenomenon Secondary to Systemic SclerosisLink: https://clinicaltrials.gov/ct2/show/NCT04848220
Conditions:Microvascular ObstructionLink: https://clinicaltrials.gov/ct2/show/NCT00619931
Conditions:Healthy
Title:Safety Study of APD-791 With Aspirin and/or Clopidogrel
Status:Terminated
updateDate:2019-02-15
Ctid:NCT02034292
Link: https://clinicaltrials.gov/ct2/show/NCT02034292
Conditions:Acute Coronary SyndromeLink: https://clinicaltrials.gov/ct2/show/NCT02419820
Conditions:Acute Coronary SyndromeLink: https://clinicaltrials.gov/ct2/show/NCT00529646
Conditions:HealthyProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
