| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
YM348 selectively targets the serotonin 5-HT2C receptor, a G protein-coupled receptor expressed primarily in the brain, including the hypothalamus. It has a Ki of 0.89 nM for the human 5-HT2C receptor and an EC50 of 1 nM, making it a potent agonist. It exhibits 15-fold selectivity over the 5-HT2A receptor. Activation of the 5-HT2C receptor by YM348 leads to downstream signaling pathways that regulate appetite and energy expenditure.
|
|---|---|
| ln Vitro |
YM348 exhibits a high affinity of 0.89 nM for the cloned human 5-HT2C receptor and a low affinity of 2.5 nM for the cloned human 5-HT2B and 13 nM for the cloned human 5-HT2A receptors. An thorough evaluation was conducted on 46 binding sites, which included various other 5-HT receptor subtypes (1A, 1B, 1D, 3, 4, 5A, 6, 7) in order to assess the binding specificity of YM348. The human 5-HT1A receptor (Ki: 130 nM), human 5-HT7 receptor (Ki: 177 nM), and bovine 5-HT1D receptor (Ki: 481 nM) are the exceptions. At human 5-HT2A and 5-HT2B receptors, YM348 demonstrates complete agonistic action. YM348's EC50 values for the 5-HT2C, 5-HT2A, and 5-HT2B receptors are, respectively, 1.0, 93, and 3.2 nM[1].
In vitro, YM348 is a potent and selective 5-HT2C receptor agonist with an EC50 of 1 nM and 15-fold selectivity over 5-HT2A. It shows high affinity for the cloned human 5-HT2C receptor with a Ki of 0.89 nM. In cell-based assays, YM348 activates 5-HT2C receptor-mediated signaling, such as phospholipase C activation and calcium mobilization. Its selectivity for 5-HT2C over 5-HT2A is important to avoid psychiatric side effects associated with 5-HT2A activation. |
| ln Vivo |
The selective 5-HT2C receptor antagonist SB242084 totally blocked the penile erection and hypokinesia that rats experienced after oral YM348 treatment. A minimum effective dose of 0.203 mg/kg is required for YM348 to reduce spontaneous activity in a dose-dependent manner [1].
In vivo, YM348 has thermogenic and anorectic effects in animal studies. It reduces food intake and increases energy expenditure, leading to weight loss. These effects are mediated through activation of 5-HT2C receptors in the hypothalamus, which regulate appetite and satiety. The compound is orally active, making it a candidate for the treatment of obesity. Its effects are dose-dependent and can be blocked by 5-HT2C receptor antagonists. |
| Enzyme Assay |
Non-cellular in vitro assays for YM348 involve receptor binding studies. A standard protocol uses membrane preparations from cells expressing recombinant human 5-HT2C receptors. The membranes are incubated with a radiolabeled ligand, such as [³H]mesulergine, and varying concentrations of YM348. Non-specific binding is determined in the presence of an excess of unlabeled mesulergine. After incubation, the reaction is terminated by rapid filtration, and the radioactivity bound to the membranes is measured. The Ki values are calculated from the competition curves.
|
| Cell Assay |
Cellular assays for YM348 are performed using cell lines expressing 5-HT2C receptors, such as CHO cells or HEK293 cells stably transfected with the receptor. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4) and then stimulated with varying concentrations of YM348. The increase in intracellular calcium concentration is measured using a fluorescence plate reader. The EC50 for calcium mobilization is determined from the concentration-response curve. The selectivity for 5-HT2C over 5-HT2A can be confirmed using cells expressing 5-HT2A receptors.
|
| Animal Protocol |
In vivo animal studies for YM348 are conducted in rodent models of obesity, such as diet-induced obese (DIO) mice. Animals are administered YM348 orally at doses such as 0.1-3 mg/kg. Food intake is measured at various time points post-administration. Body weight is monitored over longer treatment periods (e.g., 2-4 weeks). Energy expenditure is measured using indirect calorimetry. The compound's effects on thermogenesis and food intake are assessed. The involvement of 5-HT2C receptors is confirmed using selective antagonists.
|
| ADME/Pharmacokinetics |
YM348 has a molecular weight of 243.30 g/mol and a molecular formula of C14H17N3O. It is orally active, indicating good oral bioavailability. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. The compound is typically stored as a powder at -20°C. Detailed pharmacokinetic parameters, such as half-life, Cmax, and AUC, have not been fully reported in the available literature.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for YM348 have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling YM348, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.
|
| References |
[1]. Kimura Y, et al. Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C receptor agonist. Eur J Pharmacol. 2004 Jan 1;483(1):37-43
|
| Additional Infomation |
YM348 is a potent, selective, and orally active 5-HT2C receptor agonist. It has a Ki of 0.89 nM for the human 5-HT2C receptor and an EC50 of 1 nM, with 15-fold selectivity over 5-HT2A. It has thermogenic and anorectic effects in animal studies, making it a potential candidate for the treatment of obesity. The compound is not a clinically approved drug and has not entered clinical trials. Its primary application is in research on appetite regulation and obesity.
|
| Molecular Formula |
C14H17N3O
|
|---|---|
| Molecular Weight |
243.31
|
| Exact Mass |
243.137
|
| CAS # |
372163-84-3
|
| PubChem CID |
3045225
|
| Appearance |
Light yellow to brown oil
|
| Density |
1.28g/cm3
|
| Boiling Point |
395.2ºC at 760 mmHg
|
| Flash Point |
192.8ºC
|
| Index of Refraction |
1.652
|
| LogP |
3.392
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
18
|
| Complexity |
299
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H](N)CN(N=C1)C2=C1C=CC3=C2C=C(CC)O3
|
| InChi Key |
QLOOWOVVZLBYHU-VIFPVBQESA-N
|
| InChi Code |
InChI=1S/C14H17N3O/c1-3-11-6-12-13(18-11)5-4-10-7-16-17(14(10)12)8-9(2)15/h4-7,9H,3,8,15H2,1-2H3/t9-/m0/s1
|
| Chemical Name |
(2S)-1-(7-ethylfuro[2,3-g]indazol-1-yl)propan-2-amine
|
| Synonyms |
YM 348 YM-348YM348
|
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~100 mg/mL (~411.02 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.28 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: ≥ 2.5 mg/mL (10.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1100 mL | 20.5499 mL | 41.0998 mL | |
| 5 mM | 0.8220 mL | 4.1100 mL | 8.2200 mL | |
| 10 mM | 0.4110 mL | 2.0550 mL | 4.1100 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
