SR 48692
(Synonyms: 2-[[[1-(7-氯-4-喹啉基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-基]羰基]氨基]-金刚烷-2-羧酸) 目录号 : GC13242SR 48692（Meclinertant）是一种口服可生物利用的神经降压素受体NTS1的变构拮抗剂（Kd=3.4nM）。
Cas No.:146362-70-1
Sample solution is provided at 25 µL, 10mM.
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SR 48692 (Meclinertant) is an orally bioavailable, allosteric antagonist of the neuropeptide Y receptor NTS1 (Kd=3.4nM)[1, 2]. SR 48692 is the first non-peptide antagonist developed for NTS1, used in scientific research to explore the interactions of neuropeptide Y with other neurotransmitters in the brain[3]. SR 48692 enhances the sensitivity of ovarian cancer cells and experimental tumors to carboplatin[4]. SR 48692, when administered chronically via a central cannula to the paraventricular nucleus (PVN) of the hypothalamus, effectively attenuated the increase in central HPA axis activity caused by circadian rhythm fluctuations and stress responses[5].
In vitro, treatment of A375 melanoma cells with SR 48692 (5μM) for 1-4 days significantly inhibited neuropeptide-induced cell proliferation, inducing cell cycle arrest and apoptosis[6]. SR 48692 (5μM) also antagonized neuropeptide-induced increases in cytosolic Ca2+ in NCI-H209 cells[7].
In vivo, oral administration of SR 48692 (25mg/kg/day) for 5 days significantly inhibited tumor growth in mice bearing human prostate cancer cells (PC-3M-Luc cells) xenografts, and showed synergistic anti-tumor activity when combined with radiotherapy[8].
References:
[1] Gully D, Canton M, Boigegrain R, et al. Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor[J]. Proceedings of the National Academy of Sciences, 1993, 90(1): 65-69.
[2] Labbe-Jullie C, Botto J M, Mas M V, et al. [3H] SR 48692, the first nonpeptide neurotensin antagonist radioligand: characterization of binding properties and evidence for distinct agonist and antagonist binding domains on the rat neurotensin receptor[J]. Molecular pharmacology, 1995, 47(5): 1050-1056.
[3] Iyer M R, Kunos G. Therapeutic approaches targeting the neurotensin receptors[J]. Expert Opinion on Therapeutic Patents, 2021, 31(5): 361-386.
[4] Liu J, Agopiantz M, Poupon J, et al. Neurotensin receptor 1 antagonist SR48692 improves response to carboplatin by enhancing apoptosis and inhibiting drug efflux in ovarian cancer[J]. Clinical Cancer Research, 2017, 23(21): 6516-6528.
[5] Rowe W B, Nicot A, Sharma S, et al. Central administration of the neurotensin receptor antagonist, SR48692, modulates diurnal and stress-related hypothalamic-pituitary-adrenal activity[J]. Neuroendocrinology, 1997, 66(2): 75-85.
[6] Zhang Y, Zhu S, Yi L, et al. Neurotensin receptor1 antagonist SR48692 reduces proliferation by inducing apoptosis and cell cycle arrest in melanoma cells[J]. Molecular and cellular biochemistry, 2014, 389(1): 1-8.
[7] Moody T W, Chiles J, Casibang M, et al. SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells[J]. Peptides, 2001, 22(1): 109-115.
[8] Valerie N C K, Casarez E V, DaSilva J O, et al. Inhibition of neurotensin receptor 1 selectively sensitizes prostate cancer to ionizing radiation[J]. Cancer research, 2011, 71(21): 6817-6826.
SR 48692（Meclinertant）是一种口服可生物利用的神经降压素受体NTS1的变构拮抗剂（Kd=3.4nM）[1, 2]。SR 48692是首个为NTS1开发的非肽拮抗剂，用于科学研究中探索神经肽Y与大脑中其他神经递质的相互作用[3]。SR 48692增强了卵巢癌细胞和实验性肿瘤对卡铂的敏感性[4]。SR 48692通过植入中央导管慢性输注至下丘脑室旁核（PVN），有效减弱了昼夜节律波动和应激反应所引起的中枢HPA活动升高[5]。
在体外，SR 48692（5μM）处理A375黑色素瘤细胞1-4天，显著抑制了神经肽素（NTS）引起的细胞增殖，诱导了细胞周期阻滞和细胞凋亡[6]。SR 48692（5μM）处理NCI-H209 细胞，拮抗了神经肽（NT）引起的胞质Ca2+升高的能力[7]。
在体内，SR 48692（25mg/kg/day）通过口服治疗人前列腺癌细胞（PC-3M-Luc细胞）异种移植小鼠5天，显著抑制了小鼠体内肿瘤生长，与放射治疗联合使用产生协同抗肿瘤活性[8]。
| Cell experiment [1]: | |
Cell lines | A375 melanoma cells |
Preparation Method | A375 melanoma cells were treated with 0.01μM neurotensin (NTS) and 0.01μM+5μM SR 48692 seprately, DMSO was used as a control. OD570nm was measured daily from 1 to 4 days. |
Reaction Conditions | 5μM; 1-4 days |
Applications | SR48692 can inhibit cell proliferation induced by NTS. |
| Animal experiment [2]: | |
Animal models | Male athymic nude mice |
Preparation Method | Human PC-3M-luc-C6 cells were used in an orthotopic xenograft model in male athymic nude mice. Surgery was conducted to expose the prostate, and 20μL of the tumor cell suspension (5×105 cells) was injected into the dorsolateral lobe of the prostate gland. Following closure, mice were treated with SR 48692 (25mg/kg in PEG800) or vehicle control for 5 consecutive days. Drug was administered orally in 0.2mL volumes 4h prior to radiation treatments. Mice were then anesthetized with a ketamine/xylazine mix, and a dose of 2.5 Gy X-ray was given to the prostate area while shielding the body with lead. Animals were imaged on a weekly basis by anesthetizing with isoflurane before and during imaging and injecting intraperitoneally with luciferin. Animals were imaged at a peak time of 10 to 20min post-luciferin injection via a Xenogen IVIS instrument, using exposure times and sensitivity settings to avoid saturation. Image processing was conducted using Living Image software (Xenogen) by region-of-interest analysis of total photons/sec for each tumor, with appropriate background subtraction. |
Dosage form | 25mg/kg/day; 5 days; p.o. |
Applications | Combined treatment of SR 48692 with radiation elicits synergistic antitumor activity against PC-3M tumor xenografts in mice. |
References: | |
| Cas No. | 146362-70-1 | SDF | |
| 别名 | 2-[[[1-(7-氯-4-喹啉基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-基]羰基]氨基]-金刚烷-2-羧酸 | ||
| 化学名 | (1R,2R,3R,5S,7S)-2-(1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carboxamido)adamantane-2-carboxylic acid | ||
| Canonical SMILES | ClC1=CC=C2C(N3N=C(C=C3C(C(OC)=CC=C4)=C4OC)C(N[C@]5(C(O)=O)[C@H]6C[C@H]7C[C@H]5C[C@H](C7)C6)=O)=CC=NC2=C1 | ||
| 分子式 | C32H31ClN4O5 | 分子量 | 587.07 |
| 溶解度 | DMSO: 20 mM | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7034 mL | 8.5169 mL | 17.0337 mL |
| 5 mM | 340.7 μL | 1.7034 mL | 3.4067 mL |
| 10 mM | 170.3 μL | 851.7 μL | 1.7034 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；
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2.
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- Purity: >98.00%
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