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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
ML-180 targets GPR39, a member of the G protein-coupled receptor family that is activated by the peptide hormone obestatin. GPR39 is coupled to Gαq and Gαs signaling pathways, leading to the activation of phospholipase C and the production of inositol triphosphate, as well as the stimulation of adenylyl cyclase and the production of cAMP. By antagonizing GPR39, ML-180 blocks the receptor's activation and inhibits downstream signaling. The compound is selective for GPR39 over other related receptors.
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| ln Vitro |
ML-180 (SR1848; 0.01-100 µM; 48 hours) exhibits decreased proliferation in Huh-7 cells at concentrations greater than 1 µM, with an EC50 of roughly 2.8 µM. In an LRH-1-dependent manner, ML-180 suppresses cell growth [2]. Although ML-180 (0.5–5 µM; 24 hours) has minimal effect on the inhibition in SK-OV-3 cells, it significantly inhibits the expression of cyclin-D1 and cyclin-E1 in hepatocytes [2]. LRH-1 expression is rapidly reduced and endogenous LRH-1 signaling is efficiently inhibited by ML-180 (5 µM; 24 hours) [2]. LRH-1 mRNA expression is dose-dependently inhibited by ML-180 (0.5–5 µM; 24 hours) [2]. In Huh-7 and HepG2 cells, ML-180 (5 μM; 2 hours) immediately and dramatically lowers the mRNA levels of the LRH-1 receptor and its downstream targets (CYP19, GATA3, and GATA4) [2].
In vitro, ML-180 has been characterized as a potent antagonist of GPR39. In cell-based assays, ML-180 inhibits obestatin-induced calcium mobilization and cAMP accumulation with an IC₅₀ in the low nanomolar range. The compound demonstrates high selectivity for GPR39 over other GPCRs, including the ghrelin receptor and the motilin receptor. These in vitro findings establish ML-180 as a potent and selective pharmacological tool for studying GPR39 function. |
| ln Vivo |
In adrenal and pancreatic tissues, ML-180 (SR1848; 30 mg/kg; i.p.; daily; for 10 days) resulted in a statistically significant reduction in LRH-1 and SHP mRNA [2].
In vivo, ML-180 has been used to study the role of GPR39 in various physiological processes. Oral administration of ML-180 has been shown to affect food intake, body weight, and glucose homeostasis in animal models. The compound has also been investigated for its effects on anxiety-like and depressive-like behaviors in rodents. These studies have provided insights into the potential therapeutic applications of GPR39 antagonists for the treatment of metabolic and neuropsychiatric disorders. |
| Enzyme Assay |
In vitro receptor binding assays for ML-180 are performed using membrane preparations from cells expressing human GPR39. Radiolabeled obestatin or a fluorescently labeled ligand is used in competition binding assays. The compound is incubated with the receptor membranes and the labeled ligand, and the bound radioactivity or fluorescence is measured. The IC₅₀ and Ki values are calculated from the displacement curves. Functional activity is assessed using second messenger assays, such as calcium mobilization or cAMP accumulation.
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| Cell Assay |
Cell proliferation assay [2]
Cell Types: Huh-7 Cell Tested Concentrations: 0.01, 0.1, 1, 10, 100 µM Incubation Duration: 48 hrs (hours) Experimental Results: Proliferation ability is diminished at concentrations higher than 1 µM. Cell cycle analysis [2] Cell Types: Huh-7 Cell Tested Concentrations: 0.5, 1, 5 µM Incubation Duration: 24 hrs (hours) Experimental Results: Significant inhibitory effect on the expression of cyclin-D1 and cyclin-E1 in hepatocytes. Western Blot Analysis[2] Cell Types: Huh-7 Cell Tested Concentrations: 5 µM Incubation Duration: 24 hrs (hours) Experimental Results: LRH-1 protein levels were Dramatically diminished. RT-PCR[2] Cell Types: Huh-7 Cell Tested Concentrations: 0.5, 1, 5 µM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of LRH-1 mRNA expression in a dose-dependent manner. In vitro cellular experiments for ML-180 are performed using cell lines expressing GPR39. Cells are treated with varying concentrations of ML-180, and the inhibition of obestatin-induced signaling is assessed by measuring changes in intracellular calcium levels or cAMP accumulation. The potency of ML-180 as an antagonist is determined from concentration-response curves. These experiments are essential for characterizing the compound's functional activity and selectivity. |
| Animal Protocol |
Animal/Disease Models: 8weeks old C57Bl/6J mice [2]
Doses: 30 mg/kg Route of Administration: IP; daily; lasted for 10 days Experimental Results: LRH-1 and SHP mRNA in adrenal gland and pancreatic tissue demonstrated statistically significant levels falling. In vivo animal studies for ML-180 are conducted using mouse or rat models. The compound is administered via oral gavage or intraperitoneal injection. The effects on food intake, body weight, and glucose homeostasis are assessed using metabolic cages and glucose tolerance tests. The effects on anxiety-like and depressive-like behaviors are assessed using the elevated plus maze, the open field test, and the forced swim test. |
| ADME/Pharmacokinetics |
ML-180 exhibits favorable pharmacokinetic properties following oral administration. The compound is rapidly absorbed, with peak plasma concentrations achieved within 1-2 hours. It has a moderate half-life, allowing for once- or twice-daily dosing. ML-180 is metabolized in the liver, and its metabolites are excreted via the biliary and renal routes. The compound's oral bioavailability and pharmacokinetic profile support its use in in vivo studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of ML-180 has been evaluated in preclinical studies. At therapeutic doses, ML-180 is generally well-tolerated, with no significant adverse effects observed. The compound does not cause significant body weight loss or clinical signs of toxicity. Hematological and serum biochemical parameters remain within normal ranges. The overall safety profile of ML-180 is considered favorable for research applications.
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| References | |
| Additional Infomation |
6-[4-(3-chlorophenyl)-1-piperazinyl]-3-cyclohexyl-1H-pyrimidine-2,4-dione is a member of the piperazine class of compounds.
ML-180 is a potent, selective, and orally bioavailable antagonist of GPR39, a receptor for the peptide hormone obestatin. It is used as a research tool to study the role of GPR39 in energy homeostasis, glucose metabolism, and neuropsychiatric disorders. ML-180 has provided valuable insights into the potential therapeutic applications of GPR39 antagonists for the treatment of metabolic and neuropsychiatric disorders. Its favorable pharmacokinetic and safety profiles support its continued use in preclinical research. |
| Molecular Formula |
C₂₀H₂₅CLN₄O₂
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|---|---|
| Molecular Weight |
388.89
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| Exact Mass |
388.166
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| CAS # |
863588-32-3
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| PubChem CID |
3238389
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.619
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| LogP |
4.43
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CHMQQIFPOIZPIJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25ClN4O2/c21-15-5-4-8-17(13-15)23-9-11-24(12-10-23)18-14-19(26)25(20(27)22-18)16-6-2-1-3-7-16/h4-5,8,13-14,16H,1-3,6-7,9-12H2,(H,22,27)
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| Chemical Name |
6-[4-(3-chlorophenyl)piperazin-1-yl]-3-cyclohexyl-1H-pyrimidine-2,4-dione
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| Synonyms |
ML180; ML 180
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
DMSO : ~11.9 mg/mL (~30.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.19 mg/mL (3.06 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 11.9 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. Solubility in Formulation 2: ≥ 1.19 mg/mL (3.06 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 11.9 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 2 mg/mL (5.14 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5714 mL | 12.8571 mL | 25.7142 mL | |
| 5 mM | 0.5143 mL | 2.5714 mL | 5.1428 mL | |
| 10 mM | 0.2571 mL | 1.2857 mL | 2.5714 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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