| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
5-HT4 Receptor 44 nM (EC50)
5-HT4 receptor (partial agonist, EC50=44 nM) |
|---|---|
| ln Vitro |
In enzymatic assays, Usmarapride demonstrates potent 5-HT4 receptor partial agonism with an EC50 of 44 nM. It shows balanced physicochemical and pharmacokinetic properties.
|
| ln Vivo |
In the object recognition test (ORT), usmarapride (SUVN-D4010) (1-3 mg/kg; po; male Wistar rats 10–12 weeks old) reduces the long-term memory deficits[1]. Scopolamine-induced amnesia is considerably reversed by usmarapride (1, 3, and 10 mg/kg; po)[1]. At 3.0 mg/kg, usmarapride has a statistically significant impact on the recognition index and exploration time[1]. Good oral exposures, good absorption, and good cerebral exposures are demonstrated by usmarapride (SUVN-D4010) in rats[1]. Pharmacokinetics of Usmarapride in Rats[1]: F% Cmax (ng/mL), AUC (ng· hr/mL), t1/2 (h), Vdss (L/kg), CL (mLg/min/kg) 34 360 709 1.7 8.0 76
In the object recognition test (ORT) in male Wistar rats, Usmarapride (1-3 mg/kg, p.o.) reduces long-term memory deficits and significantly reverses scopolamine-induced amnesia at 1, 3 and 10 mg/kg. At 3 mg/kg, it shows statistically significant effects on recognition index and exploration time. |
| Enzyme Assay |
Receptor binding is typically performed using membrane preparations from cells expressing human 5-HT4 receptors. Radioligand displacement assays with [3H]-GR113808 determine binding affinity. For agonist activity, GTPgammaS binding or cAMP accumulation assays measure functional activation. Test compounds are incubated with membranes at varying concentrations to calculate EC50 values.
|
| Cell Assay |
Cell-based functional assays using HEK-293 or CHO cells stably expressing human 5-HT4 receptors are employed. Cells are seeded in 96-well plates and treated with serial dilutions of Usmarapride. Agonist activity is measured by quantifying intracellular cAMP accumulation via ELISA or HTRF. EC50 is calculated from concentration-response curves.
|
| Animal Protocol |
In vivo efficacy is evaluated in male Wistar rats (10-12 weeks old) using the object recognition test (ORT) for memory and scopolamine-induced amnesia models. Usmarapride is administered orally at 1-10 mg/kg. Behavioral parameters including recognition index and exploration time are recorded. Pharmacokinetic blood and brain samples are collected for exposure analysis.
|
| ADME/Pharmacokinetics |
In rats, Usmarapride demonstrates good oral absorption and brain exposure with oral bioavailability of 34%. Pharmacokinetic parameters include Cmax of 360 ng/mL, AUC of 709 ng·hr/mL, t1/2 of 1.7 h, Vdss of 8.0 L/kg, and CL of 76 mL/min/kg. It exhibits favorable physicochemical and PK properties suitable for CNS indications.
|
| Toxicity/Toxicokinetics |
Usmarapride shows a favorable nonclinical safety profile in standard preclinical studies. No significant off-target liabilities have been reported at therapeutic doses. Long-term toxicity studies typically include 28-day and 90-day repeat-dose toxicology in rodents and non-rodents to assess target organ toxicity, as is standard for CNS drug candidates.
|
| References |
[1]. Nirogi, Ramakrishna; Mohammed, Abdul Rasheed; Yarlgadda, Suresh; Ravella, Srinivasa Rao; Shinde, Anil Karbhari; Kambhampati, Ramasastri; Roayalley, Praveen Kumar; Jayarajan, Pradeep; Bhyrapuneni, Gopinadh; Patnala, Sriramachandra Murthy; et al. Preparatio
|
| Additional Infomation |
Usmarapride is an investigational drug candidate targeting the 5-HT4 receptor for Alzheimer's disease-related cognitive deficits. Its mechanism involves partial agonism at 5-HT4 receptors, which enhances cholinergic and glutamatergic neurotransmission. As of current information, it has not yet received regulatory approval and remains in preclinical or early clinical research stages.
|
| Molecular Formula |
C23H31N5O6
|
|---|---|
| Molecular Weight |
473.52
|
| Exact Mass |
473.227
|
| CAS # |
1428862-33-2
|
| Related CAS # |
Usmarapride free base;1428862-32-1
|
| PubChem CID |
71508290
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
34
|
| Complexity |
557
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C(C2C3=C([H])C([H])=C([H])C([H])=C3N(C([H])(C([H])([H])[H])C([H])([H])[H])N=2)=NN=C1C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C1([H])[H].O([H])C(C(=O)O[H])=O
|
| InChi Key |
XHXCJKNEBFAUSE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H29N5O2.C2H2O4/c1-15(2)26-18-8-5-4-7-17(18)19(24-26)21-23-22-20(28-21)16-9-12-25(13-10-16)11-6-14-27-3;3-1(4)2(5)6/h4-5,7-8,15-16H,6,9-14H2,1-3H3;(H,3,4)(H,5,6)
|
| Chemical Name |
2-[1-(3-methoxypropyl)piperidin-4-yl]-5-(1-propan-2-ylindazol-3-yl)-1,3,4-oxadiazole;oxalic acid
|
| 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: 33.33 mg/mL (70.39 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.28 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 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: ≥ 2.5 mg/mL (5.28 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 25.0 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: ≥ 2.5 mg/mL (5.28 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 | 2.1118 mL | 10.5592 mL | 21.1184 mL | |
| 5 mM | 0.4224 mL | 2.1118 mL | 4.2237 mL | |
| 10 mM | 0.2112 mL | 1.0559 mL | 2.1118 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
