BMY 7378
(Synonyms: BMY7378抑制剂) 目录号 : GC10848
BMY 7378是一种α1D-肾上腺素能受体（α1D-AR）的选择性拮抗剂，pki值为8.89，也是血清素1A受体（5-HT1A R）的混合激动剂和拮抗剂。
Cas No.:21102-95-4
Sample solution is provided at 25 µL, 10mM.
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BMY 7378 is a selective antagonist of α1D-adrenergic receptor (α1D-AR) with a pki value of 8.89. It is also a mixed agonist and antagonist of serotonin 1A receptor (5-HT1A R)[1, 2]. BMY 7378 can inhibit angiotensin converting enzyme and has antihypertensive activity[3].
In vitro, BMY 7378 (10nM, 10μM) treatment of AC01 cells significantly inhibited norepinephrine (NA)-induced inositol [1,4,5] triphosphate (IP3) production[4].
In vivo, oral treatment of spontaneously hypertensive rats (SHR) with BMY 7378 (10mg/kg/day) for 4 weeks significantly reduced the blood pressure of the treated rats, improved cardiac myocyte fibrosis and cardiac hypertrophy, and increased the expression of α1D-AR protein[5]. BMY 7378 (5mg/kg) was administered to adult male hamsters via surgically implanted osmotic minipumps for 28 days, which upregulated the mRNA of 5-HT1A and 5-HT1B receptors in the hamster hypothalamus, downregulated the mRNA of 5-HT1A and monoamine oxidase-A in the brainstem, and altered the behavioral circadian rhythm of the hamsters[6].
References:
[1] Chen J. Characterisation of novel alpha1-adrenoceptor ligands[D]. UNSW Sydney, 2014.
[2] Jeffers R. The Involvement of the Intergeniculate Leaflet in the Potentiation of Photic Phase Shifts by the 5-HT1A Mixed Agonist/Antagonist BMY 7378[J]. 2013.
[3] Rodríguez J E, Andrade-Jorge E, Barquet-Nieto A, et al. BMY 7378, a selective α1D-adrenoceptor antagonist, is a new angiotensin converting enzyme inhibitor: In silico, in vitro and in vivo approach[J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 2025, 1869(1): 130732.
[4] Ohmi K, Shinoura H, Nakayama Y, et al. Characterization of α1‐adrenoceptors expressed in a novel vascular smooth muscle cell line cloned from p53 knockout mice, P53LMAC01 (AC01) cells[J]. British journal of pharmacology, 1999, 127(3): 756-762.
[5] Rodríguez J E, Saucedo-Campos A D, Vega A V, et al. The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats[J]. Journal of Hypertension, 2020, 38(8): 1496-1503.
[6] Vijaya Shankara J, Orr A, Mychasiuk R, et al. Chronic BMY 7378 treatment alters behavioral circadian rhythms[J]. European Journal of Neuroscience, 2017, 46(11): 2782-2790.
BMY 7378是一种α1D-肾上腺素能受体（α1D-AR）的选择性拮抗剂，pki值为8.89，也是血清素1A受体（5-HT1A R）的混合激动剂和拮抗剂[1, 2]。BMY 7378能够抑制血管紧张素转换酶，具有抗高血压活性[3]。
在体外，BMY 7378（10nM，10μM）处理AC01细胞，显著抑制了去甲肾上腺素（NA）诱导的肌醇[1,4,5]三磷酸（IP3）产生[4]。
在体内，BMY 7378（10mg/kg/day）通过口服治疗自发性高血压大鼠（SHR）4周，显著降低了治疗组大鼠的血压，改善心脏心肌细胞的纤维化和心脏肥大，增加了α1D-AR蛋白的表[5]。BMY 7378（5mg/kg）通过手术植入的渗透微型泵对成年雄性仓鼠进行给药28天，上调了仓鼠下丘脑中5-HT1A受体和5-HT1B受体的mRNA，下调了脑干中5-HT1A和单胺氧化酶-A的mRNA，改变了仓鼠的行为昼夜节律[6]。
| Animal experiment [1]: | |
Animal models | Spontaneously hypertensive rats (SHR) |
Preparation Method | Thirty-week-old spontaneously hypertensive rats (SHR) were treated for 4 weeks with BMY 7378 (10mg/kg per day, p.o.), or captopril (angiotensin-converting enzyme inhibitor, 40mg/kg per day, p.o.) (as a positive control). Blood pressure and cardiac function were measured in vivo, cardiac hypertrophy by histology, and α1D-AR protein expression by immunofluorescence. |
Dosage form | 10mg/kg/day; 4 weeks; p.o. |
Applications | BMY 7378 and captopril decreased blood pressure and improved hemodynamic parameters and cardiac function in treated SHR vs. untreated SHR. Histology showed increased cardiomyocyte size, fibrosis, and left ventricular hypertrophy in SHR hearts. BMY 7378 ameliorated fibrosis and cardiac hypertrophy, but had no effect on cardiomyocyte size in SHR. Effects of BMY 7378 were associated with increased α1D-AR protein expression in SHR. |
References: | |
| Cas No. | 21102-95-4 | SDF | |
| 别名 | BMY7378抑制剂 | ||
| 化学名 | 8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione;dihydrochloride | ||
| Canonical SMILES | COC1=CC=CC=C1N2CCN(CC2)CCN3C(=O)CC4(CCCC4)CC3=O.Cl.Cl | ||
| 分子式 | C22H31N3O3.2HCl | 分子量 | 458.42 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 25 mg/ml,Ethanol: 0.2 mg/ml,PBS (pH 7.2): 0.5 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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| 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 | 2.1814 mL | 10.907 mL | 21.8141 mL |
| 5 mM | 0.4363 mL | 2.1814 mL | 4.3628 mL |
| 10 mM | 0.2181 mL | 1.0907 mL | 2.1814 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet