ML221 |
Katalog-Nr.GC14855
One-Click Copy Product Info
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ML 221 ist ein potenter funktioneller Antagonist von Apelin (APJ), der die Apelin-13-vermittelte Aktivierung von APJ hemmt, mit IC50s von 0,70 μM im cAMP-Assay und 1,75 μM im β-Arrestin-Assay und EC80 von 10 nM in beiden Assays .
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 877636-42-5
Sample solution is provided at 25 µL, 10mM.
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ML221 is a selective, reversible antagonist of the apelin receptor (APJ)[1]. APJ is a G protein-coupled receptor homologous to the angiotensin II receptor, widely expressed in cardiovascular, nervous, and metabolic tissues, mediating the hypotensive, positive inotropic, and angiogenic effects triggered by apelin peptides[2]. ML221 is commonly used for research into the mechanisms of cardiovascular diseases, metabolic syndrome, and renal fibrosis[3].
In vitro, ML221 (10–20μM; 24h) significantly reduced HTR8/SVneo cell migration, invasion, and tube formation, and attenuated primary extravillous trophoblasts (EVTs) migration and invasion enhanced by COL6A1 overexpression[4]. ML221 (10μM; 15min) significantly inhibited apelin-induced reductions in ROS production and increases in SOD activity in SHR cardiomyocytes[5].
In vivo, ML221 (10mg/kg; i.p.; 7 days) restored BTB integrity, increased TJP1 and GJA1 expression, and improved sperm quality and fertilization rates in db/db mice[6]. ML221 (150μg/kg; 14 days; i.p.) reversed letrozole-induced polycystic ovarian morphology in adult Swiss albino mice, reduced cyst number, restored corpus luteum formation, lowered serum testosterone and androstenedione, and normalized the LH/FSH ratio[7].
References:
[1] Maloney PR, Khan P, Hedrick M, et al. Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor. Bioorg Med Chem Lett. 2012;22(21):6656-6660.
[2] Antushevich H, Wójcik M. Review: Apelin in disease. Clin Chim Acta. 2018;483:241-248.
[3] Wang Y, Wang Y, Xue K, Gao F, Li C, Fang H. Elevated reactivity of Apelin inhibited renal fibrosis induced by chronic intermittent hypoxia. Arch Biochem Biophys. 2021;711:109021.
[4] Qi G, Gong Y, Li Y, et al. Insufficient expression of COL6A1 promotes the development of early-onset severe preeclampsia by inhibiting the APJ/AKT signaling pathway. Cell Death Discov. 2025;11(1):81.
[5] Yeves AM, Godoy Coto J, Pereyra EV, et al. Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium. J Physiol Biochem. 2024;80(4):949-959.
[6] Song K, Yang X, An G, et al. Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models. Nat Commun. 2022;13(1):7335.
[7] Anima B, Gurusubramanian G, Roy VK. Apelin receptor modulation mitigates letrozole-induced polycystic ovarian pathogenesis in mice. Cytokine. 2024;179:156639.
| Cell experiment [1]: | |
Cell lines | Rat ventricular myocytes |
Preparation Method | Rat ventricular myocytes were isolated from hearts mounted in a Langendorff apparatus. The treatments for fresh cardiomyocytes were: (1) Control, (2) Apelin 50nM, (3) Apelin+ML221(10μM). ML221, when used, was added 5min before IGF-1 or apelin. After 10min, ROS production and NO production were measured. |
Reaction Conditions | 10μM; 15min |
Applications | ML221 significantly inhibited apelin-induced reductions in ROS production in SHR cardiomyocytes. |
| Animal experiment [2]: | |
Animal models | female Swiss albino mice |
Preparation Method | 20 adult virgin female Swiss albino mice of 2–3 months of age and average weight of 25g, were used for this study and were kept in a laboratory condition (12h light: 12h dark cycle, at 25±2℃). Food and water were provided ad libitum. Mice were randomly grouped into four; (i) Control (Con) group (n=5) was given 100μL of saline (vehicle) orally, (ii) Letrozole-treated group (PCOS) (n=5) received letrozole orally at a concentration of 1mg/kg daily for 21 days, (iii) Letrozole + apelin treated (PCOS+AP) (n=5) group, was received letrozole orally at a concentration of 1mg/kg daily for 21 days plus apelin intraperitoneal injection at a dose of 100μg/kg for 14 days and (iv) Letrozole+apelin inhibitor ML221 (PCOS+ML221) (n=5) group was received letrozole orally at a concentration of 1mg/kg daily for 21 days plus intraperitoneal injection of ML221 at a dose of 150μg/kg for 14 days. Body weight was taken every day before treatment during the experiment. The estrous cycle of the mice was observed for the confirmation of PCOS condition through vaginal smear. On day 36th of the experiment, all the mice were sacrificed under mild anesthesia and body weight was recorded before sacrificed. Ovaries were dissected out without any adhering fat tissue immediately after being sacrificed and ovary weight was recorded. One of the ovaries from each group was fixed in Bouin’s solution for histology and immunohistochemistry analysis. The other ovaries were kept at −20℃ for western blotting. The serum sample was collected and stored at −20℃ for hormonal assays and metabolic parameters quantification. |
Dosage form | 150μg/kg; 14 days; i.p. |
Applications | ML221 reversed letrozole-induced polycystic ovarian morphology in adult Swiss albino mice, reduced cyst number, restored corpus luteum formation, lowered serum testosterone and androstenedione, and normalized the LH/FSH ratio. |
References: | |
| Cas No. | 877636-42-5 | SDF | |
| Chemical Name | 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate | ||
| Canonical SMILES | O=C(C(OC(C1=CC=C(N(=O)=O)C=C1)=O)=CO2)C=C2CSC3=NC=CC=N3 | ||
| Formula | C17H11N3O6S | M.Wt | 385.35 |
| Löslichkeit | DMF: 10 mg/ml,DMF:PBS (pH 7.2) (1:30): 0.03 mg/ml,DMSO: 1 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.595 mL | 12.9752 mL | 25.9504 mL |
| 5 mM | 519 μL | 2.595 mL | 5.1901 mL |
| 10 mM | 259.5 μL | 1.2975 mL | 2.595 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)