PF-06256142
目录号 : GC65343
PF-06256142 是一种高效、选择性的，中枢神经系统穿透性的，具有口服活性的 D1 受体 (D1 receptor) 激动剂，其 EC50 和 Ki 值分别为 33 nM 和 12 nM。PF-06256142 有用于精神分裂症和阿尔茨海默症研究的潜力。
Cas No.:1609583-14-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
HumanD1Receptor 33nM(EC50) |
PF-06256142 is a potent, selective, CNS-penetrant and orally active agonist of the D1 receptor, with an EC50 and Ki of 33 nM and 12 nM, respectively. PF-06256142 has the potential for the research of schizophrenia and Parkinson's disease[1].
PF-06256142 exhibits IC50 values of 10 μM)[1].
PF-06256142 exhibits high oral bioavailability (rat 85%) following oral administration (rat 5 mg/kg)[1].PF-06256142 exhibits terminal elimination half-life (rat 2.3 h) following intravenous administration (rat 5.0 mg/kg)[1].
[1]. Davoren JE, et al. Discovery and Lead Optimization of Atropisomer D1 Agonists with Reduced Desensitization. J Med Chem. 2018 Nov 15.
| Cas No. | 1609583-14-3 | SDF | Download SDF |
| 分子式 | C21H16N4O2S | 分子量 | 388.44 |
| 溶解度 | DMSO : 200 mg/mL (514.88 mM; Need ultrasonic) | 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 | 2.5744 mL | 12.872 mL | 25.744 mL |
| 5 mM | 0.5149 mL | 2.5744 mL | 5.1488 mL |
| 10 mM | 0.2574 mL | 1.2872 mL | 2.5744 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。
Discovery and Lead Optimization of Atropisomer D1 Agonists with Reduced Desensitization
J Med Chem 2018 Dec 27;61(24):11384-11397.PMID:30431269DOI:10.1021/acs.jmedchem.8b01622
The discovery of D1 subtype-selective agonists with drug-like properties has been an enduring challenge for the greater part of 40 years. All known D1-selective agonists are catecholamines that bring about receptor desensitization and undergo rapid metabolism, thus limiting their utility as a therapeutic for chronic illness such as schizophrenia and Parkinson's disease. Our high-throughput screening efforts on D1 yielded a single non-catecholamine hit PF-4211 (6) that was developed into a series of potent D1 receptor agonist leads with high oral bioavailability and CNS penetration. An important structural feature of this series is the locked biaryl ring system resulting in atropisomerism. Disclosed herein is a summary of our hit-to-lead efforts on this series of D1 activators culminating in the discovery of atropisomer 31 (PF-06256142), a potent and selective orthosteric agonist of the D1 receptor that has reduced receptor desensitization relative to dopamine and other catechol-containing agonists.