| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EC50: 3.7 μM (Apelin receptor)[1]
ML233 is a potent agonist of the apelin receptor (APJ, also known as APLNR) with an EC50 of 3.7 uM. It demonstrates >21-fold selectivity over the angiotensin 1 (AT1) receptor (>79 uM). More recently, ML233 was also discovered to directly inhibit the enzyme tyrosinase. |
|---|---|
| ln Vitro |
ML233 exhibits potentially significant binding to a number of additional receptors, such as the norepinephrine transporter, benzylpiperazine, α2C adrenergic, and 5-HT1A receptors. Human hepatocytes exhibit some toxicity towards ML233 (LC50=25.8 μM)[1].
ML233 shows potent APJ agonism in vitro (EC50 = 3.7 uM). It has been shown to inhibit tyrosinase function in vitro, reducing melanin production in murine melanoma cells. Additionally, it exhibits potentially significant binding to several other receptors, including 5-HT1A, alpha2C adrenergic, and benzylpiperazine receptors, as well as the norepinephrine transporter. |
| ln Vivo |
Intraperitoneal administration of ML233 (1-5 mg/kg) has been shown to suppress neuronal cell death in mouse models of NMDA-induced retinal damage and ischemia-reperfusion injury. Furthermore, it inhibits melanin production in zebrafish larvae, a standard in vivo model for pigmentation, with no observable significant toxic side effects.
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| Enzyme Assay |
ML233's binding affinity for the apelin receptor (APJ) can be determined using standard GPCR radioligand binding assays, which involve incubating cell membranes expressing APJ with a radiolabeled ligand (e.g., [125I]-apelin-13) and increasing concentrations of ML233.
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| Cell Assay |
Functional APJ agonism is assessed using cell-based assays measuring downstream signaling, such as inhibition of forskolin-stimulated cAMP production or measurement of beta-arrestin recruitment. For its tyrosinase inhibitory activity, B16F10 murine melanoma cells are cultured and treated with ML233, followed by quantification of melanin content to determine the IC50 of inhibition.
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| Animal Protocol |
In mouse models of NMDA-induced retinal damage, mice received intraperitoneal injections of ML233 (1 or 5 mg/kg). The percentage of retinal ganglion cells (RGCs) was measured to assess the protective effect. In zebrafish models of pigmentation, embryos were treated with ML233, and melanin levels were quantified.
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| ADME/Pharmacokinetics |
Comprehensive pharmacokinetic data for ML233 is limited. It is stable for long-term storage at -20degC as a powder and for up to 1 year in solution at -80degC. It is formulated in DMSO for in vitro use; for in vivo injection, typical formulations include DMSO, Tween 80, and saline. Cytotoxicity was observed against human hepatocytes (LC50 = 25.8 uM).
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| Toxicity/Toxicokinetics |
In vivo, ML233 shows no observable significant toxic side effects in zebrafish models.
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| References |
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| Additional Infomation |
ML233 is a research-grade chemical and not approved for clinical use. Its primary applications are as a tool to study the apelin/APJ system in the CNS and retina, and as a potential lead for developing new therapies for pigmentation disorders and melanoma, as it was found to inhibit melanin production via direct tyrosinase inhibition, independent of the apelin pathway.
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| Molecular Formula |
C19H21NO4S
|
|---|---|
| Molecular Weight |
359.439344167709
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| Exact Mass |
359.119
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| CAS # |
2080311-92-6
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| PubChem CID |
46905036
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
700
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C=C(C)/C(=N\OS(=O)(=O)C2C=CC=CC=2)/C=C1C1CCCCC1
|
| InChi Key |
RSMZOLWJZGIWOV-ZZEZOPTASA-N
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| InChi Code |
InChI=1S/C19H21NO4S/c1-14-12-19(21)17(15-8-4-2-5-9-15)13-18(14)20-24-25(22,23)16-10-6-3-7-11-16/h3,6-7,10-13,15H,2,4-5,8-9H2,1H3/b20-18-
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| Chemical Name |
[(Z)-(5-cyclohexyl-2-methyl-4-oxocyclohexa-2,5-dien-1-ylidene)amino] benzenesulfonate
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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)
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| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7821 mL | 13.9105 mL | 27.8211 mL | |
| 5 mM | 0.5564 mL | 2.7821 mL | 5.5642 mL | |
| 10 mM | 0.2782 mL | 1.3911 mL | 2.7821 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.
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