ghrelin receptor ( Ki = 0.7 nM ); ghrelin receptor ( EC50 = 0.74 nM )

在 FLIPR 测定中，Anamorelin (ANAM) 对 ghrelin 受体表现出显着的激动剂活性，EC50 值为 0.74 nM。 Anamorelin 在浓度高达 1,000 nM 时未观察到显着的拮抗剂活性。在结合实验中，Anamorelin 与生长素释放肽受体结合，结合亲和常数 (Ki) 为 0.70 nM。在放射性标记的伊丁莫伦竞争测定中，还发现 Anamorelin (ANAM) 与生长素释放肽受体具有高亲和力结合 (IC50=0.69 nM)。在与 Anamorelin 一起孵育的大鼠垂体细胞中，对 GH 释放有剂量依赖性刺激作用，效力 (EC50) 为 1.5 nM。 Anamorelin 经过针对 100 多种受体、离子通道、转运蛋白和酶的活性筛选。 Anamorelin 与速激肽神经激肽 2 (NK2) 位点结合 (IC50=0.021 μM)；然而，随后的 NK2 功能测定显示没有功能活性[1]。

在大鼠中，与载体对照相比，每日一次口服剂量 3、10 或 30 mg/kg 的 Anamorelin (ANAM) 从治疗第 2 天到第 7 天显着增加食物摄入量和体重。食物摄入量和体重增加的累积变化随剂量而增加，与对照相比，这些变化在所有剂量水平上都很显着（P<0.05）。单次口服剂量 3、10 或 30 mg/kg 的 Anamorelin 会引起大鼠血浆 GH 水平和 GH AUC0-6h 剂量依赖性增加[1]。

在竞争测定中，膜补充了³⁵S-MK-677 和浓度范围为 1 pM 至 10 μM 的阿拉莫林 (ANAM)。为了确定非特异性结合，添加 10 μM 未标记的 MK-677。将样品施加到已用 0.5% PEI 预处理的 GF/B 过滤器上，并将混合物在 30°C 下孵育 60 分钟。在 0.9% NaCl 中清洗后，使用 OptiPhase 计数器对过滤器进行计数 [1]。

Rats: Rats are separated into four groups for the purpose of assessing food intake and body weight: Anamorelin 3 mg/kg (n = 7), 10 mg/kg (n = 7), or 30 mg/kg (n = 7), or vehicle control (n = 8). 100 μL blood samples are taken prior to and 0.25, 0.5, 1, 2, 3, 4, 5, and 6 hours following a single dose. Rats are put to sleep using a 64.8 mg/kg dose of sodium pentobarbital. In order to collect blood, a catheter equipped with a three-way cock to allow extra blood to return, an extension tube, and a 1 mL sampling syringe is placed inside the left femoral artery and filled with heparinized saline solution. A Rat Growth Hormone EIA kit and microplate reader are used to immunochemically measure the levels of growth hormone in plasma. There are two measurement takes place. The time course of GH plasma concentrations is assessed, as well as the area under the GH concentration curve from 0 to 6 hours (A_UC0-6h) postdose.
Pig: Anamorelin is administered intraperitoneally (IDI) using a dosing catheter to six groups of pigs each. Blood is drawn for the GH stimulation profile at 15, 30, 45, 60, and 120 minutes after dosing, as well as at 30 and 15 minutes before. The animals were given either a single dose (3.5 mg/kg) or a once-daily administration (1 mg/kg) of anamorelin for seven days. Following the first and seventh doses, stimulation profiles were taken. In order to measure IGF-1 levels, pigs are given either a placebo or anamorelin (1 mg/kg/day) for seven days, after which they switch between the two treatments for an additional seven days. Every day, right before the dose, a single blood sample is obtained.

[1]. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexiasyndrome: preclinical profile. J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):329-37.

C31H42N6O3

546.70359

546.33

C, 63.85; H, 7.43; Cl, 6.08; N, 14.41; O, 8.23

249921-19-5

Anamorelin hydrochloride; 861998-00-7; Anamorelin Fumarate; 339539-92-3; 249921-19-5

white to off-white solid powder

CC(C)(C(=O)N[C@H](CC1=CNC2=CC=CC=C21)C(=O)N3CCC[C@](C3)(CC4=CC=CC=C4)C(=O)N(C)N(C)C)N

VQPFSIRUEPQQPP-MXBOTTGLSA-N

InChI=1S/C31H42N6O3/c1-30(2,32)28(39)34-26(18-23-20-33-25-15-10-9-14-24(23)25)27(38)37-17-11-16-31(21-37,29(40)36(5)35(3)4)19-22-12-7-6-8-13-22/h6-10,12-15,20,26,33H,11,16-19,21,32H2,1-5H3,(H,34,39)/t26-,31-/m1/s1

2-amino-N-[(2R)-1-[(3R)-3-benzyl-3-[dimethylamino(methyl)carbamoyl]piperidin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-methylpropanamide

ONO7643; ONO-7643; ONO 7643; RC 1291; RC1291; RC-1291

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~182.9 mM)
Ethanol: ~50 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。