Cycloleucine
(Synonyms: 环亮氨酸) 目录号 : GC61751
Cycloleucine是一种S-腺苷甲硫氨酸介导的甲基化的特异性抑制剂，通过竞争性结合甲基转移酶活性位点来阻断多种生物分子的甲基化修饰过程。Cycloleucine是N-甲基-D-天冬氨酸（NMDA）受体甘氨酸变构位点的拮抗剂，Ki值为600μM，具有抗焦虑作用。
Cas No.:52-52-8
Sample solution is provided at 25 µL, 10mM.
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Cycloleucine is a specific inhibitor of S-adenosylmethionine-mediated methylation, which blocks the methylation modification process of various biological molecules by competitively binding to the active site of methyltransferases[1]. Cycloleucine is an antagonist of the glycine allosteric site of the N-methyl-D-aspartate (NMDA) receptor with a Ki value of 600μM and has an anxiolytic effect[2, 3]. Cycloleucine is also a competitive inhibitor of ATP:L-methionine-S-adenosyltransferase in vitro, which can interfere with the biosynthesis of S-adenosylmethionine (SAM), thereby affecting the supply of methyl donors[4]. Cycloleucine can significantly inhibit plant growth, resulting in the disappearance of plant apical dominance, a significant decrease in plant height and dry weight, the retardation of leaf hair development on the back, and the inhibition of net photosynthetic rate and the activity of key enzymes in the Calvin cycle[5].
In vitro, treatment of rat hepatocytes with Cycloleucine (20mM) for 24 or 48h significantly reduced intracellular S-adenosyl-L-methionine (SAM) levels and induced hepatocyte cytotoxicity[6]. Treatment of RAW cells with Cycloleucine (40 mM) for 2h depleted intracellular SAM[7].
In vivo, intracerebroventricular administration of Cycloleucine (0.5, 1, 2, 4µg) to rats with bilateral nucleus accumbens (NAS) cannulation increased the time the rats spent in the open arm, the time they entered the open arm, and the time they reached the extreme end of the arm in the elevated plus maze test[8].
References:
[1] Ma C, Xu A, Zuo L, et al. Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential[J]. Pharmaceuticals, 2025, 18(5): 640.
[2] Hershkowitz N, Rogawski M A. Cycloleucine blocks NMDA responses in cultured hippocampal neurones under voltage clamp: antagonism at the strychnine‐insensitive glycine receptor[J]. British journal of pharmacology, 1989, 98(3): 1005-1013.
[3] Gottlieb A, Stein G Y, Ruppin E, et al. PREDICT: a method for inferring novel drug indications with application to personalized medicine[J]. Molecular systems biology, 2011, 7(1): 496.
[4] Caboche M, Hatzfeld J. Methionine metabolism in BHK cells: preliminary characterization of the physiological effects of cycloleucine, an inhibitor of S‐adenosylmethionine biosynthesis[J]. Journal of Cellular Physiology, 1978, 97(3): 361-370.
[5] Niu T, Zhang J, Li J, et al. Effects of exogenous glycine betaine and cycloleucine on photosynthetic capacity, amino acid composition, and hormone metabolism in Solanum melongena L[J]. Scientific Reports, 2023, 13(1): 7626.
[6] Zhuge J, Cederbaum A I. Depletion of S-adenosyl-l-methionine with cycloleucine potentiates cytochrome P450 2E1 toxicity in primary rat hepatocytes[J]. Archives of biochemistry and biophysics, 2007, 466(2): 177-185.
[7] Song Z, Chen T, Deaciuc I V, et al. Modulation of endotoxin stimulated interleukin-6 production in monocytes and Kupffer cells by S-adenosylmethionine (SAMe)[J]. Cytokine, 2004, 28(6): 214-223.
[8] Gargiulo A P I, Acuña A, Gargiulo M M L, et al. Effects of cycloleucine in the nucleus accumbens septi on the elevated plus maze test in rats[J]. Neuropsychobiology, 2020, 79(3): 191-197.
Cycloleucine是一种S-腺苷甲硫氨酸介导的甲基化的特异性抑制剂，通过竞争性结合甲基转移酶活性位点来阻断多种生物分子的甲基化修饰过程[1]。Cycloleucine是N-甲基-D-天冬氨酸（NMDA）受体甘氨酸变构位点的拮抗剂，Ki值为600μM，具有抗焦虑作用[2, 3]。Cycloleucine在体外也是ATP:L-蛋氨酸-S-腺苷基转移酶的竞争性抑制剂，能够干扰S-腺苷甲硫氨酸（SAM）的生物合成，从而影响甲基供体的供应[4]。Cycloleucine能够明显抑制植物的生长，导致植物顶端优势消失，株高和干鲜重明显下降，背面叶毛发育受阻，净光合速率和卡尔文循环关键酶活性受到抑制[5]。
在体外，Cycloleucine（20mM）处理大鼠肝细胞24或48h，显著降低了细胞内S-腺苷-L-蛋氨酸（SAM）的水平，诱导了肝细胞的细胞毒性[6]。Cycloleucine（40mM）处理RAW细胞2h，细胞内SAM被耗尽[7]。
在体内，Cycloleucine（0.5, 1, 2, 4µg）通过脑室内注射治疗双侧伏隔核（NAS）插管处理的大鼠，在高架十字迷宫试验中增加了大鼠在开放臂中停留的时间、开放臂进入时间和极端到达时间[8]。
| Cell experiment [1]: | |
Cell lines | Hepatocytes |
Preparation Method | 5×106 hepatocytes were seeded in 15cm culture dishes and treated with 0 or 20mM Cycloleucine for 24 or 48h. The hepatocytes were washed twice with PBS and scraped, centrifuged at 80×g for 10min, and the cell pellet was dispersed with 120μL of 0.1M KPi (pH 7.4). 5μL was used for protein concentration analysis, and the remaining cell suspension was added to 120μL of 0.4M HClO4, mixed thoroughly, and centrifuged at 12,000rpm for 10min at 4°C. The supernatant was filtered and S-Adenosyl-L-methionine (SAM) levels were measured by high-performance liquid chromatography. |
Reaction Conditions | 20mM; 24, 48h |
Applications | Treatment with 20mM Cycloleucine for 24 or 48h dramatically decreased SAM levels to 30% those of non-treated control hepatocytes. |
| Animal experiment [2]: | |
Animal models | Rats of a Holtzman-derived colony |
Preparation Method | The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1µL injections of saline or Cycloleucine (0.5, 1, 2, or 4µg) 15min before testing. After testing completion, rats were injected with saturated methylene blue solution (1µL). They were sacrificed with an excess of ether 15min later. Brains were removed from the skull. Afterwards, they were fixed in 20% formalin solution. |
Dosage form | 0.5, 1, 2, 4µg; 1µL; i.c.v. |
Applications | Treatment with Cycloleucine produced increases in the time spent in the open arm. Open arm entries were increased by the higher dose, and extreme arrivals were increased by all doses. Time spent in the open arm is recognized as the most classical parameter of an anxiolytic effect. |
References: | |
| Cas No. | 52-52-8 | SDF | |
| 别名 | 环亮氨酸 | ||
| Canonical SMILES | O=C(O)C1(CCCC1)N | ||
| 分子式 | C6H11NO2 | 分子量 | 129.16 |
| 溶解度 | Water: 50 mg/mL (387.12 mM); DMSO: < 1 mg/mL (ultrasonic) (insoluble or slightly soluble) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 7.7423 mL | 38.7117 mL | 77.4234 mL |
| 5 mM | 1.5485 mL | 7.7423 mL | 15.4847 mL |
| 10 mM | 0.7742 mL | 3.8712 mL | 7.7423 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 | ||||||||||
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工作液浓度： mg/ml；
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2.
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