PF-06649751
(Synonyms: PF-06649751; CVL-751) 目录号 : GC48598
A dopamine D1 and D5 receptor partial agonist
Cas No.:1643489-24-0
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
PF-06649751 is a dopamine D1 and D5 receptor partial agonist.1 It increases locomotor activity and reduces a global parkinsonian disability score in a macaque model of Parkinson's disease induced by MPTP when administered at a dose of 0.04 mg/kg.
1.Young, D., Popiolek, M., Trapa, P., et al.D1 agonist improved movement of parkinsonian nonhuman primates with limited dyskinesia side effectsACS Chem. Neurosci.11(4)560-566(2020)
| Cas No. | 1643489-24-0 | SDF | |
| 别名 | PF-06649751; CVL-751 | ||
| Canonical SMILES | O=C1NC(N(C)C(C2=C(C)C=C(OC3=NC=CC=C3C(F)(F)F)C=C2)=C1C)=O | ||
| 分子式 | C19H16F3N3O3 | 分子量 | 391.3 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:20): 0.05 mg/ml,Ethanol: 2 mg/ml | 储存条件 | -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 | 2.5556 mL | 12.7779 mL | 25.5558 mL |
| 5 mM | 0.5111 mL | 2.5556 mL | 5.1112 mL |
| 10 mM | 0.2556 mL | 1.2778 mL | 2.5556 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。
PF-06649751 efficacy and safety in early Parkinson's disease: a randomized, placebo-controlled trial
Ther Adv Neurol Disord 2020 Mar 6;13:1756286420911296.PMID:32201505DOI:10.1177/1756286420911296.
Background: PF-06649751 is a novel, oral, non-catechol-based, D1/D5 dopamine receptor partial agonist under investigation for the treatment of motor symptoms associated with Parkinson's disease. Methods: A 15-week, phase II, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy and safety of flexible-dose PF-06649751 in subjects with early stage Parkinson's disease (ClinicalTrials.gov identifier: NCT02847650). Results: Enrollment was terminated early for reasons unrelated to the trial. Overall, 57 subjects received study medication (PF-06649751 = 29; placebo = 28) and 47 completed the study (PF-06649751 = 25; placebo = 22). Despite early termination, the study met its primary endpoint with the PF-06649751 group showing statistically significant improvement from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score at week 15 compared with placebo. Mean (SE) change in MDS-UPDRS Part III score was -9.0 (1.54) for PF-06649751 and -4.3 (1.65) for placebo. This corresponds to an improvement versus placebo of 4.8 for the PF-06649751 group (two-sided p = 0.0407; 90% CI = 1.0, 8.6). Statistically significant improvement in MDS-UPDRS-III score was also observed at all assessment time points prior to week 15. The safety profile of PF-06649751 was similar to that observed in prior studies, with the majority of adverse events (AEs) reported as mild or moderate. The most common AEs in the PF-06649751 group were nausea, headache, dry mouth, somnolence, and tremor. Conclusions: Once-daily dosing of oral PF-06649751 resulted in significant improvement of motor symptoms and was generally well tolerated in subjects with early stage Parkinson's disease.
Phase 1 Parkinson's Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated
Neurol Ther 2018 Dec;7(2):307-319.PMID:30361858DOI:10.1007/s40120-018-0114-z.
Introduction: There is a need for new therapies in Parkinson's disease that may help to address known limitations of current options. PF-06649751 is a novel, highly selective dopamine D1/D5 agonist targeted for Parkinson's disease treatment. Methods: The safety, pharmacokinetics, and pharmacodynamics of PF-06649751 were assessed in single ascending dose and multiple ascending dose clinical trials in patients with Parkinson's disease. The single ascending dose study (N = 18) was a double-blind, placebo-controlled study with a three-way crossover design consisting of three treatment periods separated by 7-day study drug washout periods. PF-06649751 doses were 0.75 mg, 1.5 mg, 3 mg, 6 mg, and 9 mg. In the open-label multiple ascending dose study, eligible subjects received once-daily doses of PF-06649751 (N = 45) over 21 days, with up-titration to 5 mg, 15 mg, and 25 mg once daily. Pharmacodynamics were assessed by measuring change from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at different time points post dose. Results: PF-06649751 was safe and well tolerated across studies and in all cohorts. Peak plasma concentrations were attained 1-4 h post dose across both studies, and exposure increased with increasing dose. PF-06649751 demonstrated sustained pharmacodynamic effects compared with placebo, with mean reductions from baseline in the MDS-UPDRS Part III up to 12 h post dose at 9 mg single dose. MDS-UPDRS Part III changes in the open-label multiple dose study on day 22 also demonstrated sustained pharmacodynamic activity. Conclusions: PF-06649751 represents a novel therapeutic candidate for Parkinson's disease with an initial safety, tolerability, and pharmacokinetic profile and potential for efficacy that merits further study in larger clinical trials. Trial registration: These studies are registered at www.clinicaltrials.gov as NCT02373072, NCT02224664. Funding: Pfizer.
D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited Dyskinesia Side Effects
ACS Chem Neurosci 2020 Feb 19;11(4):560-566.PMID:31971364DOI:10.1021/acschemneuro.9b00589.
Parkinson's disease is a progressive neurodegenerative disease characterized by striatal dopaminergic loss. L-DOPA treatment replaces lost dopamine and enables motor function; however, eventually, fluctuating efficacy and side effects associated with its use become challenging for many patients. Here, we demonstrate, in a clinically translatable nonhuman primate model of parkinsonian motor symptoms, that treatment with the partial D1 receptor agonist CVL-751, formerly known as PF-06649751, is just as effective as L-DOPA in enabling movement and reducing disability. Importantly, CVL-751 efficacy is observed with less of the concomitant dyskinesia side effect associated with L-DOPA treatment. Data presented suggest that partial D1 agonists may be an effective and important treatment strategy for the management of Parkinson's patients.