ML221
目录号 : GC14855
ML221是apelin受体APJ的选择性可逆拮抗剂。
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.
ML221是apelin受体APJ的选择性可逆拮抗剂[1]。APJ是一种与血管紧张素II受体同源的G蛋白偶联受体，广泛表达于心血管神经和代谢组织，介导apelin肽引发的降压正性肌力和血管新生效应[2]。ML221常用于心血管疾病代谢综合征和肾纤维化机制研究[3]。
体外实验中，ML221（10-20μM；24h）显著抑制HTR8/SVneo细胞迁移、侵袭和管腔形成，并减弱COL6A1过表达所增强的原代绒毛外滋养层细胞迁移与侵袭[4]。在SHR心肌细胞中，ML221（10μM；15min）显著抑制apelin诱导的ROS产生减少和SOD活性的增加[5]。
体内实验中，ML221（10mg/kg；腹腔注射；7天）恢复db/db小鼠的血睾屏障完整性，上调TJP1和GJA1表达，改善精子质量及受精率[6]。ML221（150μg/kg; 14天；腹腔注射）改善了成年瑞士白化小鼠的多囊卵巢形态，减少了囊肿数量，恢复了黄体形成，降低了血清睾酮和雄烯二酮水平，并使LH/FSH比值恢复正常[7]。
| 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 | |
| 化学名 | 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 | ||
| 分子式 | C17H11N3O6S | 分子量 | 385.35 |
| 溶解度 | DMF: 10 mg/ml,DMF:PBS (pH 7.2) (1:30): 0.03 mg/ml,DMSO: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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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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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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- Purity: >99.50%
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