| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
mAChR3 15 nM (Ki) mAChR1 28 nM (Ki) mAChR2 260 nM (Ki)
M1, M2, and M3 muscarinic acetylcholine receptors (mAChRs). YM-58790 is a potent antagonist at these receptor subtypes. |
|---|---|
| ln Vitro |
Compound 18b (YM-58790 free base) (0-1 μM) has no effect on bradycardia but a strong inhibitory effect on the contraction of the bladder. In vitro, YM-58790 demonstrates a specific antagonistic relationship between salivary secretion and bladder contraction[1].
YM-58790 free base is a potent mAChR antagonist that inhibits M1, M2, and M3 mAChRs with Ki values of 28 nM, 260 nM, and 15 nM, respectively. This profile indicates potent antagonist activity at M1 and M3 receptors, with relatively lower affinity for the M2 subtype. |
| ln Vivo |
The tremor in mice generated by oxotremorine is not affected by YM-58790 free base (3 mg/kg, iv)[1]. With an ED30 value of 0.36 mg/kg (iv) and an ID50 value of 2.4 mg/kg (iv), YM-58790 free base (6.0 mg/kg; iv) exhibits strong efficacy on M3 antagonism but demonstrates inadequate M1 and M2 antagonism impact in vivo on McN-A343-induced pressor in pitted rats[1]. Similar to oxybutynin, YM-58790 free base has strong inhibitory activity on bladder pressuer in reflexively-evoked rhythmic contraction. However, in rats, it has an inhibitory impact on oxotremorine-induced salivary secretion that is about ten times less effective than oxybutynin[1].
In vivo, YM-58790 free base inhibits reflex rhythmic bladder contractions in rats by inhibiting bladder pressurization. This effect is consistent with the role of M3 receptors in mediating bladder smooth muscle contraction. The compound's antagonist activity at M3 receptors is likely responsible for its inhibitory effects on bladder function. Its higher potency at M3 (Ki = 15 nM) compared to M2 (Ki = 260 nM) suggests that it may have a favorable profile for treating bladder dysfunction with reduced cardiovascular side effects associated with M2 antagonism. |
| Enzyme Assay |
In vitro receptor binding assays are performed to determine the affinity of YM-58790 for M1, M2, and M3 mAChRs. Radioligand binding studies using membrane preparations from cells or tissues expressing the target receptors are conducted. The compound's ability to displace a specific radiolabeled ligand from each receptor subtype is measured to calculate its Ki values.
|
| Cell Assay |
In vitro cell-based assays are conducted using cells expressing recombinant M1, M2, or M3 mAChRs. The cells are treated with a receptor agonist in the presence or absence of varying concentrations of YM-58790. The inhibition of agonist-induced intracellular signaling, such as calcium mobilization or PI hydrolysis, is measured to quantify the antagonistic activity. The potency of YM-58790 at each receptor subtype is determined from these functional assays.
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| Animal Protocol |
In vivo studies are conducted in animal models to evaluate the effects of YM-58790 on bladder function. The compound is administered to rats, and its effects on reflex rhythmic bladder contractions are assessed by measuring bladder pressure. The inhibition of bladder pressurization is used as a measure of the compound's efficacy in modulating bladder function. Dosing regimens are determined based on preliminary dose-response studies.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for YM-58790 free base. As a research compound, its ADME properties would be characterized in standard preclinical studies to guide in vivo experiments. The compound's oral bioavailability, half-life, and tissue distribution are key parameters for understanding its pharmacological effects.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for YM-58790 free base. As a mAChR antagonist, its toxicity profile is expected to be related to its mechanism of action, potentially affecting cholinergic signaling in peripheral and central nervous systems. Standard safety assessments would be required for any therapeutic development.
|
| References |
[1]. Naito R, et al. Selective muscarinic antagonists. I. Synthesis and antimuscarinic properties of 4-piperidyl benzhydrylcarbamate derivatives. Chem Pharm Bull (Tokyo). 1998 Aug;46(8):1274-85.
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| Additional Infomation |
YM-58790 free base is a potent mAChR antagonist with activity at M1, M2, and M3 receptors. It has been studied for its potential therapeutic applications in conditions involving bladder dysfunction, such as overactive bladder and urinary incontinence. The compound is a 4-piperidyl benzhydrylcarbamate derivative and is not approved for human therapeutic use.
|
| Molecular Formula |
C27H31N3O2
|
|---|---|
| Exact Mass |
429.241
|
| CAS # |
168830-70-4
|
| Related CAS # |
YM-58790;214558-72-2
|
| PubChem CID |
9888883
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
32
|
| Complexity |
525
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CNC1=CC=C(C=C1)CN2CCC(CC2)OC(=O)NC(C3=CC=CC=C3)C4=CC=CC=C4
|
| InChi Key |
YLHJUSKJLHTVJY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H31N3O2/c1-28-24-14-12-21(13-15-24)20-30-18-16-25(17-19-30)32-27(31)29-26(22-8-4-2-5-9-22)23-10-6-3-7-11-23/h2-15,25-26,28H,16-20H2,1H3,(H,29,31)
|
| Chemical Name |
[1-[[4-(methylamino)phenyl]methyl]piperidin-4-yl] N-benzhydrylcarbamate
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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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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