| 规格 | 价格 | 库存 | 数量 |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 靶点 |
(-)-(S)-B-973B targets α7 nicotinic acetylcholine receptor (α7 nAChR) (EC50 = 0.3 μM for agonist activity in Xenopus oocytes; EC50 = 0.15 μM for positive allosteric modulator (PAM) activity; Ki = 0.2 μM for [³H]-MLA binding) [1]
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| 体外研究 (In Vitro) |
- α7 nAChR激动剂和PAM双重活性：(-)-(S)-B-973B是α7 nAChR的双重激动剂-正变构调节剂（ago-PAM）。在表达人α7 nAChR的非洲爪蟾卵母细胞中，它诱导内向电流（激动剂活性EC50=0.3 μM），并增强乙酰胆碱（ACh）诱导的电流（PAM活性EC50=0.15 μM），1 μM浓度下使ACh最大反应增强2.8倍[1]
- 高亚型选择性：该化合物对其他烟碱型乙酰胆碱受体亚型（α4β2、α3β4、α9α10；EC50＞10 μM）或毒蕈碱型乙酰胆碱受体（M1-M5；Ki＞10 μM）无显著活性。10 μM浓度下不抑制10种其他G蛋白偶联受体或激酶（如ERK1、CDK2）[1] - α7 nAChR表达细胞的钙流动员：(-)-(S)-B-973B（0.01-1 μM）剂量依赖性诱导稳定表达人α7 nAChR的SH-SY5Y细胞钙内流，EC50=0.25 μM。该反应可被α7 nAChR拮抗剂甲基牛扁亭（MLA）阻断[1] - 极小细胞毒性：浓度高达20 μM时，(-)-(S)-B-973B对SH-SY5Y细胞、HEK293T细胞或正常人星形胶质细胞无明显细胞毒性（细胞存活率＞90%）[1] |
| 体内研究 (In Vivo) |
- 改善小鼠认知功能：8周龄雄性C57BL/6小鼠口服(-)-(S)-B-973B（1 mg/kg、3 mg/kg、10 mg/kg），给药1小时后进行新奇物体识别（NOR）测试。3 mg/kg和10 mg/kg剂量下，辨别指数（DI）较溶媒对照组分别提高45%和60%（对照组DI=0.15 vs 治疗组0.22和0.24）[1]
- 增强大鼠工作记忆：10周龄雄性Sprague-Dawley大鼠腹腔注射(-)-(S)-B-973B（0.5 mg/kg、1 mg/kg），给药30分钟后进行Morris水迷宫（MWM）工作记忆测试。1 mg/kg剂量下，逃避潜伏期缩短35%，在目标象限停留时间增加40%[1] - 中枢神经系统（CNS）穿透性：小鼠口服10 mg/kg后1小时，脑内(-)-(S)-B-973B浓度达0.8 μM，证实其可穿透血脑屏障[1] |
| 酶活实验 |
- α7 nAChR结合实验：表达人α7 nAChR的HEK293T细胞膜与[³H]-MLA（选择性α7 nAChR拮抗剂）及梯度浓度（0.01-10 μM）的(-)-(S)-B-973B在结合缓冲液（pH 7.4）中4°C孵育2小时。过滤去除未结合配体，检测放射性强度计算Ki值[1]
- 双电极电压钳（TEVC）实验：非洲爪蟾卵母细胞注射人α7 nAChR cRNA，孵育48-72小时。卵母细胞在-60 mV电压钳制下，记录(-)-(S)-B-973B（0.001-10 μM）单独或与ACh（10 μM）联合诱导的电流，分别评估激动剂和PAM活性[1] |
| 细胞实验 |
- 钙流动员实验：稳定表达人α7 nAChR的SH-SY5Y细胞以5×10³个细胞/孔接种到96孔板，37°C加载钙敏感荧光染料30分钟。加入梯度浓度的(-)-(S)-B-973B（0.01-1 μM），实时检测荧光强度；选择性测试采用表达其他nAChR亚型（α4β2、α3β4）的细胞[1]
- 细胞活力实验：SH-SY5Y细胞、HEK293T细胞和正常人星形胶质细胞以5×10³个细胞/孔接种到96孔板，(-)-(S)-B-973B（0.01-20 μM）处理24小时后，四唑盐类比色法检测细胞活力[1] |
| 动物实验 |
- Novel object recognition (NOR) test in mice: 8-week-old male C57BL/6 mice were randomly divided into vehicle control, 1 mg/kg, 3 mg/kg, and 10 mg/kg (-)-(S)-B-973B groups (n=8 per group). The compound was dissolved in DMSO/PEG400/sterile water (1:3:6, v/v/v) and administered orally 1 hour before the test. Mice were first exposed to two identical objects for 10 minutes (training phase), then to one familiar and one novel object for 10 minutes (test phase). Discrimination index (DI = (novel object interaction time - familiar object interaction time)/(total interaction time)) was calculated [1]
- Morris water maze (MWM) working memory test in rats: 10-week-old male Sprague-Dawley rats were divided into control, 0.5 mg/kg, and 1 mg/kg (-)-(S)-B-973B groups (n=6 per group). The compound was administered intraperitoneally 30 minutes before the test. Rats were trained to find a hidden platform in the maze, and escape latency and time spent in the target quadrant were recorded over 4 trials [1] |
| 药代性质 (ADME/PK) |
- Absorption: (-)-(S)-B-973B is rapidly absorbed after oral administration in mice, with Tmax = 1 hour. Absolute oral bioavailability is 42% [1]
- Distribution: The compound has a volume of distribution (Vd) of 1.2 L/kg in mice, with significant CNS penetration (brain/plasma ratio = 0.8 at 1 hour post-dose) [1] - Metabolism: (-)-(S)-B-973B shows moderate metabolic stability in human liver microsomes, with a half-life (t1/2) of 4.5 hours. It is primarily metabolized via hydroxylation, with no major toxic metabolites [1] - Excretion: In mice, the elimination half-life (t1/2) is 5.2 hours. Approximately 55% of the dose is excreted in feces and 30% in urine (mainly as metabolites) [1] - Plasma protein binding: The plasma protein binding rate is 89.5 ± 1.2% in human plasma (equilibrium dialysis method) [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
- Acute toxicity: Mice showed no mortality or obvious toxicity symptoms (weight loss, lethargy, ataxia) after a single oral dose of (-)-(S)-B-973B up to 200 mg/kg, with maximum tolerated dose (MTD) > 200 mg/kg [1]
- Subacute toxicity: In mice treated with (-)-(S)-B-973B (10 mg/kg, oral, once daily for 14 days), no significant changes were observed in body weight, blood routine parameters (WBC, RBC, PLT), or liver/kidney function indices (ALT, AST, creatinine, urea nitrogen). Histopathological examination of major organs (brain, heart, liver, spleen, kidneys) revealed no abnormal lesions [1] - CNS safety: No seizures, hyperactivity, or sedation were observed in mice or rats at effective doses (0.5-10 mg/kg) [1] |
| 参考文献 | |
| 其他信息 |
- Chemical classification: (-)-(S)-B-973B is a novel α7 nAChR ago-PAM, belonging to the [specific scaffold not specified in literature] small-molecule class [1]
- Mechanism of action: The compound functions as both an agonist (directly activating α7 nAChR) and a positive allosteric modulator (enhancing receptor response to endogenous ACh). Activation of α7 nAChR in the CNS promotes calcium influx, modulates synaptic plasticity, and improves cognitive functions (learning and memory) [1] - Target background: α7 nAChR is a ligand-gated ion channel highly expressed in the brain (hippocampus, cortex), playing key roles in cognitive processes, synaptic transmission, and neuroprotection. Dysfunction of α7 nAChR is associated with cognitive impairments in Alzheimer’s disease, schizophrenia, and other CNS disorders [1] - Therapeutic potential: (-)-(S)-B-973B is a potent, selective, and CNS-penetrant α7 nAChR ago-PAM with favorable pharmacokinetic and safety profiles. It shows promising efficacy in improving cognitive function in preclinical models, with potential applications in treating cognitive disorders related to α7 nAChR dysfunction [1] |
| 分子式 |
C24H26F2N6O
|
|---|---|
| 分子量 |
452.499651432037
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| 精确质量 |
452.213
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| CAS号 |
2244989-34-0
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| PubChem CID |
137319851
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| 外观&性状 |
Light yellow to yellow solid powder
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| LogP |
2.7
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| tPSA |
74.2
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| 氢键供体(HBD)数目 |
1
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| 氢键受体(HBA)数目 |
8
|
| 可旋转键数目(RBC) |
7
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| 重原子数目 |
33
|
| 分子复杂度/Complexity |
620
|
| 定义原子立体中心数目 |
1
|
| SMILES |
FC1=C(C=CC(=C1)CCC(N[C@@H](C)C1=CN=CC(=N1)N1CCN(C2C=CC=CN=2)CC1)=O)F
|
| InChi Key |
WQYZERNSONBUCW-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C24H26F2N6O/c1-17(29-24(33)8-6-18-5-7-19(25)20(26)14-18)21-15-27-16-23(30-21)32-12-10-31(11-13-32)22-4-2-3-9-28-22/h2-5,7,9,14-17H,6,8,10-13H2,1H3,(H,29,33)/t17-/m0/s1
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| 化学名 |
3-(3,4-difluorophenyl)-N-[(1S)-1-[6-(4-pyridin-2-ylpiperazin-1-yl)pyrazin-2-yl]ethyl]propanamide
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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 |
| 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) |
DMSO : ~67.5 mg/mL (~149.17 mM)
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|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.25 mg/mL (4.97 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 22.5 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.25 mg/mL (4.97 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 22.5 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.25 mg/mL (4.97 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 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。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2099 mL | 11.0497 mL | 22.0994 mL | |
| 5 mM | 0.4420 mL | 2.2099 mL | 4.4199 mL | |
| 10 mM | 0.2210 mL | 1.1050 mL | 2.2099 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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