| 规格 | 价格 | 库存 | 数量 |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 靶点 |
Metabotropic glutamate receptor 5 (mGluR5) (EC50 = 31 nM for potentiation of glutamate-induced calcium mobilization; no affinity for other mGluR subtypes) [1]
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| 体外研究 (In Vitro) |
在表达大鼠 mGlu5 的 HEK 293 细胞中，ADX-47273（0.1 nM-10 μM；5 分钟）以浓度依赖性方式增加对 50 nM 谷氨酸的反应，而本身不引起反应[1]。 ADX-47273（0.1 nM–10 μM；5 分钟）的 EC50 为 0.23 μM，以浓度依赖性方式增加原代星形胶质细胞培养物中对 300 nM 谷氨酸的反应[1]。 ADX47273（0.01-10 μM；60 分钟）的 Ki 为 4.3 μM，可抑制 [3H]MPEP 与表达大鼠 mGlu5 受体的 HEK 细胞膜的结合[1]。
在表达人mGluR5的中国仓鼠卵巢（CHO）细胞中，ADX-47273（BA 94673139）作为正性变构调节剂（PAM），以浓度依赖方式增强谷氨酸诱导的钙动员，EC50为31 nM。无谷氨酸存在时不激活mGluR5，且对其他mGluR亚型（mGluR1-4、6-8）或离子型谷氨酸受体无显著结合[1] 在大鼠海马切片中，ADX-47273（BA 94673139）（1-10 μM）增强Schaffer侧支-CA1突触处mGluR5介导的长时程增强（LTP）——学习记忆的细胞相关性指标，该效应可被选择性mGluR5拮抗剂MPEP阻断[3] 在大鼠原代皮质神经元培养物中，ADX-47273（BA 94673139）（0.1-10 μM）以浓度依赖方式增强谷氨酸诱导的细胞外信号调节激酶（ERK）1/2磷酸化——mGluR5激活的下游信号事件[1] |
| 体内研究 (In Vivo) |
在大鼠海马和前额皮质中，ADX47273（1–10 mg/kg；单次腹腔注射）以剂量依赖性方式增加 ERK 和 CREB 的磷酸化[1]。 ADX47273（10-100 mg/kg；一次腹腔注射）以剂量依赖性方式降低大鼠的条件性回避反应[1]。在小鼠中，ADX47273（10-300 mg/kg；腹腔注射）可抑制阿扑吗啡诱导的攀爬[1]。在大鼠中，ADX47273（0.1-50 mg/kg；腹腔注射）可降低冲动性并提高五选系列反应时间测试中新物体的识别能力[1]。在使用莫里斯水迷宫 (MWM) 的小鼠中，ADX47273（15 毫克/千克；腹膜内注射）可改善逆转学习 [3]。
在大鼠中，口服ADX-47273（BA 94673139）（3-30 mg/kg）剂量依赖抑制条件回避反应（CAR）——抗精神病活性的临床前模型，ED50约为10 mg/kg。它还能在10和30 mg/kg剂量下逆转苯环利定（PCP）诱导的自发活动亢进（精神分裂症相关阳性症状模型），且不引起僵住症（典型抗精神病药的副作用）[2] 在小鼠中，口服ADX-47273（BA 94673139）（1-10 mg/kg）增强恐惧条件反射实验中的适应性学习：增加情境恐惧记忆保留率并改善消退学习，该效应可被MPEP预处理消除[3] 在大鼠中，ADX-47273（BA 94673139）（3-30 mg/kg，口服）改善Morris水迷宫实验中的工作记忆，表现为逃避潜伏期缩短和目标象限停留时间增加，证实其认知增强活性[1] |
| 酶活实验 |
CHO-hmGluR5细胞谷氨酸诱导钙动员实验：将表达人mGluR5的CHO细胞接种到96孔板培养至汇合，用钙敏感荧光染料负载细胞37°C孵育60分钟。用ADX-47273（BA 94673139）（0.1-1000 nM）预孵育细胞30分钟，再用亚最大浓度的谷氨酸（1 μM）刺激。通过酶标仪实时记录荧光强度变化，计算使谷氨酸诱导钙反应增强50%的浓度（EC50）[1]
mGluR5选择性放射性配体结合实验：从表达单个mGluR亚型（mGluR1-8）的CHO细胞制备膜匀浆，将匀浆与[3H]-MPEP（针对mGluR5）或亚型特异性放射性配体（针对其他mGluR）及ADX-47273（BA 94673139）（1 μM）孵育。通过过滤分离结合态和游离态配体，测定放射性强度并确定结合亲和力；未检测到对非mGluR5亚型的显著结合[1] |
| 细胞实验 |
海马切片LTP实验：制备300 μm厚的大鼠海马切片，在人工脑脊液（ACSF）中32°C孵育1小时。在高频刺激（100 Hz，1秒）诱导LTP前30分钟，向ACSF中加入ADX-47273（BA 94673139）（1-10 μM）。LTP诱导后记录60分钟的场兴奋性突触后电位（fEPSPs），评估突触增强效果[3]
皮质神经元ERK磷酸化检测：从胚胎大鼠大脑分离皮质神经元，接种到多聚-D-赖氨酸包被的培养板中，用神经基底培养基培养7-10天。用ADX-47273（BA 94673139）（0.1-10 μM）联合谷氨酸（0.5 μM）处理神经元5分钟。裂解细胞后，通过SDS-PAGE分离蛋白并转移至膜上，用抗磷酸化ERK和抗总ERK抗体探针杂交，密度法量化条带强度以测定ERK激活水平[1] |
| 动物实验 |
Animal/Disease Models: Male Long-Evans rats[1]
Doses: 1, 10 mg/kg Route of Administration: A single ip Experimental Results: Increased ERK and CREB phosphorylation in both the prefrontal cortex and hippocampus. Conditioned avoidance response (CAR) assay in rats: Male rats are trained in a two-compartment shuttle box to avoid foot shock by moving to the opposite compartment after a conditioned stimulus (CS). After stable CAR acquisition, ADX-47273 (BA 94673139) is suspended in 0.5% methylcellulose and administered orally at doses of 3, 10, or 30 mg/kg 60 minutes before testing. The percentage of avoidance responses and escape latency are recorded during the test session [2] PCP-induced hyperlocomotion assay in rats: Rats are habituated to activity monitors for 30 minutes, then administered ADX-47273 (BA 94673139) (3, 10, 30 mg/kg, po) or vehicle. Sixty minutes later, rats receive an intraperitoneal injection of PCP (5 mg/kg) and are returned to activity monitors. Locomotor activity (total distance traveled) is recorded for 120 minutes [2] Fear conditioning assay in mice: Male mice are subjected to contextual fear conditioning (foot shock paired with chamber context) or cued fear conditioning (foot shock paired with auditory CS). Twenty-four hours after conditioning, ADX-47273 (BA 94673139) (1, 3, 10 mg/kg, po) is administered 60 minutes before the test. Freezing behavior (a measure of fear memory) is recorded during the test session (contextual or cued) and during extinction training over consecutive days [3] |
| 药代性质 (ADME/PK) |
Oral absorption: ADX-47273 (BA 94673139) has good oral bioavailability of ~65% in rats and ~72% in mice [1]
Distribution: It distributes widely into tissues, with a volume of distribution (Vdss) of ~1.8 L/kg in rats. Brain penetration is efficient, with a brain/plasma concentration ratio of ~0.9 in rats [1] Metabolism: It is metabolized in the liver primarily via cytochrome P450 2D6 and 3A4, producing inactive metabolites [1] Excretion: The elimination half-life (t1/2) is ~4.5 hours in rats and ~3.8 hours in mice. Approximately 55% of the dose is excreted in feces and 35% in urine, with <10% excreted as unchanged drug [1] Plasma protein binding: ADX-47273 (BA 94673139) has high plasma protein binding (~92%) in rats and humans [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
Acute toxicity studies in rats and mice showed no mortality or overt toxicity at oral doses up to 200 mg/kg [1]
Subchronic toxicity study (28 days) in rats at oral doses of 10, 30, 100 mg/kg/day revealed no significant changes in body weight, food intake, hematological parameters, or liver/kidney function. Histopathological examination of major organs (liver, kidney, brain, heart) showed no abnormalities [1] |
| 参考文献 |
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| 其他信息 |
ADX-47273 (BA 94673139) is a novel, selective positive allosteric modulator (PAM) of mGluR5 [1]
Its mechanism of action involves binding to the allosteric site of mGluR5, enhancing the receptor’s response to endogenous glutamate without direct receptor activation [1] It exhibits preclinical antipsychotic-like activity (via CAR inhibition and reversal of PCP-induced hyperlocomotion) and procognitive effects (via enhancing learning and memory in animal models), supporting potential use in schizophrenia and cognitive impairment disorders [2] Unlike typical antipsychotics, it does not induce catalepsy, suggesting a favorable side effect profile [2] Its enhancement of mGluR5-mediated synaptic plasticity (LTP) contributes to its procognitive effects by strengthening neural circuits involved in learning and memory [3] |
| 分子式 |
C20H17F2N3O2
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|---|---|---|
| 分子量 |
369.36
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| 精确质量 |
369.128
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| CAS号 |
851881-60-2
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| 相关CAS号 |
(R)-ADX-47273;851881-59-9
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| PubChem CID |
11383075
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.3±0.1 g/cm3
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| 沸点 |
540.8±60.0 °C at 760 mmHg
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| 闪点 |
280.9±32.9 °C
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| 蒸汽压 |
0.0±1.4 mmHg at 25°C
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| 折射率 |
1.580
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| LogP |
3.48
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| tPSA |
59.23
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| 氢键供体(HBD)数目 |
0
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| 氢键受体(HBA)数目 |
6
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| 可旋转键数目(RBC) |
3
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| 重原子数目 |
27
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| 分子复杂度/Complexity |
508
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| 定义原子立体中心数目 |
1
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| SMILES |
C1C[C@@H](CN(C1)C(=O)C2=CC=C(C=C2)F)C3=NC(=NO3)C4=CC=C(C=C4)F
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| InChi Key |
VXQCCZHCFBHTTD-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C20H17F2N3O2/c21-16-7-3-13(4-8-16)18-23-19(27-24-18)15-2-1-11-25(12-15)20(26)14-5-9-17(22)10-6-14/h3-10,15H,1-2,11-12H2/t15-/m0/s1
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| 化学名 |
(4-fluorophenyl)-[(3S)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone
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| 别名 |
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
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| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7074 mL | 13.5369 mL | 27.0739 mL | |
| 5 mM | 0.5415 mL | 2.7074 mL | 5.4148 mL | |
| 10 mM | 0.2707 mL | 1.3537 mL | 2.7074 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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