XAP044
目录号 : GC18120XAP044是一种mGlu7选择性拮抗剂，IC50值为5.5μM。
Cas No.:196928-50-4
Sample solution is provided at 25 µL, 10mM.
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XAP044 is a potent mGlu7 selective antagonist, with an IC50 value of 5.5μM[1]. XAP044 blocks mGlu7 signaling via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding[2]. XAP044 has been widely used as a model compound for the development of a series of related derivatives to inhibit mGlu7 activity[3].
In vivo, a single subcutaneous injection of XAP044(30mg/kg) within 2 hours reversed mechanical hyperalgesia and ameliorated anxieties and depression-like behaviors in a mouse model of neuropathic pain[4]. A single intraperitoneal injection of XAP044 at a dose of 60mg/kg for 30 minutes alleviated physiological and congenital anxist-and depression-like behaviors in mice, and reduced freezing behavior during the acquisition phase of fear conditioning[5]. Intracerebroventricular infusion of 100µM XAP044 at a rate of 0.11µl/h via a micro-osmotic pump for 20 days improved hypothalamic-pituitary-adrenal axis dysfunction, thymic atrophy, and chronic subordinate colony housing (CSC)-induced increases in congenital anxiety in male C57BL/6 mice[6].
References:
[1] Fisher N M, Seto M, Lindsley C W, et al. Metabotropic glutamate receptor 7: a new therapeutic target in neurodevelopmental disorders[J]. Frontiers in molecular neuroscience, 2018, 11: 387.
[2] Palazzo E, Marabese I, Luongo L, et al. Nociception modulation by supraspinal group III metabotropic glutamate receptors[J]. Journal of Neurochemistry, 2017, 141(4): 507-519.
[3] Cristiano N, Cabayé A, Brabet I, et al. Novel inhibitory site revealed by XAP044 Mode of Action on the metabotropic glutamate 7 receptor Venus Flytrap Domain[J]. Journal of medicinal chemistry, 2024, 67(14): 11662-11687.
[4] Palazzo E, Romano R, Luongo L, et al. MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice[J]. Pain, 2015, 156(6): 1060-1073.
[5] Gee C E, Peterlik D, Neuhäuser C, et al. Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the Venus flytrap domain (VFTD) inhibits amygdala plasticity, stress, and anxiety-related behavior[J]. Journal of Biological Chemistry, 2014, 289(16): 10975-10987.
[6] Estrela K A R, Senninger L, Arndt J, et al. Blocking metabotropic glutamate receptor subtype 7 via the Venus Flytrap Domain promotes a chronic stress-resilient phenotype in mice[J]. Cells, 2022, 11(11): 1817.
XAP044是一种mGlu7选择性拮抗剂，IC50值为5.5μM[1]。XAP044通过结合于mGlu7受体的细胞外 Venus Flytrap 结构域（通常为正构激动剂结合区域）来阻断mGlu7信号传导[2]。XAP044目前已作为模型化合物广泛应用于开发抑制mGlu7活性的系列衍生物[3]。
在体内，单次皮下注射30 mg/kg剂量的XAP044可在2小时内逆转神经病理性疼痛小鼠模型的机械性痛觉过敏，并改善焦虑和抑郁样行为[4]。单次腹腔注射60mg/kg剂量的XAP044 30分钟，可缓解小鼠的生理性和先天性焦虑抑郁样行为，并减少恐惧条件反射习得阶段的僵直行为[5]。通过微型渗透泵以0.11μl/h的速率脑室输注100μM的XAP044连续20天，能改善慢性从属群体饲养（CSC）诱导的雄性C57BL/6小鼠下丘脑-垂体-肾上腺轴功能障碍、胸腺萎缩及先天性焦虑增强[6]。
| Animal experiment [1]: | |
Animal models | Male CD1 mice |
Preparation Method | Adult male CD1 mice (20-25g) were housed under controlled illumination (12:12-hour light/dark cycle; light on 6 hours) and environmental conditions (room temperature: 20°C-22°C, humidity: 55%-60%) for at least 1 week before the beginning of experiments. Chow and tap water were available ad libitum. Mechanical allodynia was evaluated 14 days after spared nerve injury (SNI) or sham surgery by the dynamic plantar aesthesiometer. Mice were allowed to freely move in 1 of the 2 compartments of the enclosure, positioned on the metal mesh surface, and allowed to adapt to the testing environment before any measurement was taken. After 30-minute habituation period, the mechanical stimulus, a steel rod (2mm) pushed with ascending force (0-30g in 10 seconds), was delivered to the plantar surface of the hind paw of the mouse from below the floor of the test chamber by an automated testing device. When the mouse withdrew the hind paw, the mechanical stimulus was automatically stopped, and the force was recorded to the nearest 0.1g. Data were expressed as mechanical withdrawal threshold (MWT) and measured for 1 hour before and for 2 hours after a single vehicle (0.05% DMSO in saline), or XAP044 (30mg/kg; s.c.) administration. |
Dosage form | 30mg/kg for once; s.c. |
Applications | XAP044 treatment reversed mechanical allodynia in mice with SNI. |
References: | |
| Cas No. | 196928-50-4 | SDF | |
| 化学名 | 7-hydroxy-3-(4-iodophenoxy)-4H-1-benzopyran-4-one | ||
| Canonical SMILES | O=C1C2=CC=C(O)C=C2OC=C1OC3=CC=C(I)C=C3 | ||
| 分子式 | C15H9IO4 | 分子量 | 380.1 |
| 溶解度 | ≤10mg/ml in ethanol;20mg/ml in DMSO;20mg/ml in dimethyl formamide | 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 | 2.6309 mL | 13.1544 mL | 26.3089 mL |
| 5 mM | 526.2 μL | 2.6309 mL | 5.2618 mL |
| 10 mM | 263.1 μL | 1.3154 mL | 2.6309 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet