PF-06447475
目录号 : GC13850
PF-06447475 是一种高效、选择性和脑渗透性 LRRK2 抑制剂，IC50 为 3 nM。
Cas No.:1527473-33-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats: PF-06447475 are administered to the desired amount in a suspension solution consisting of 10% propylene glycol, 20% PEG-400, and 70% 0.5% methylcellulose. To determine the potency of PF-06447475 in blocking brain LRRK2 kinase activity, wild-type Sprague-Dawley rats are treated at 3 and 30 mg/kg PF-06447475 (p.o. b.i.d.) for 14 days, and total and phospho-LRRK2 are subsequently measured from brain tissue lysates[3]. |
References: [1]. Henderson JL, et al. Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor. J Med Chem. 2015 Jan 8;58(1):419-32. | |
PF-06447475 is a highly potent, selective and brain penetrant LRRK2 inhibitor with an IC50 of 3 nM.
PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC50s of 3 and 25 nM, respectively[1]. Cells incubated with PF-06447475 alone (0.5, 1, 3 μM) or in the presence of ROT significantly reduces (S935)-LRRK2 kinase phosphorylation to control. PF-06447475 significantly preserves the nucleus morphology and ΔΨm of NLCs exposed to ROT compared to untreated and control. PF-475 significantly diminishes ROT-induced ROS generation to a similar extent to cells exposed to PF-475 alone[2].
In G2019S+ rats treated with PF-06447475, a significant reduction in microgliosis to levels found in wild-type rats could be observed. The proinflammatory marker MHC-II expressed on myeloid cells but not neurons also appears to be less abundant in confocal sections in G2019S+ rats treated with PF-06447475. PF-06447475 treatment in G2019S+ rats significantly lowers the number of CD68 cells recruited to the SNpc. PF-06447475 successfully blocks the enhanced neuroinflammation associated with G2019S-LRRK2 expression. Treatment of G2019S+ rats with PF-06447475 preserves TH expression in the dorsal striatum, consistent with drug attenuating neurodegeneration in the SNpc[3]. PF-06447475 is well tolerated in rats[1].
References:
[1]. Henderson JL, et al. Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor. J Med Chem. 2015 Jan 8;58(1):419-32.
[2]. Mendivil-Perez M, et al. Neuroprotective Effect of the LRRK2 Kinase Inhibitor PF-06447475 in Human Nerve-Like Differentiated Cells Exposed to Oxidative Stress Stimuli: Implications for Parkinson's Disease. Neurochem Res. 2016 Oct;41(10):2675-2692.
[3]. Daher JP, et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration. J Biol Chem. 2015 Aug 7;290(32):19433-44.
| Cas No. | 1527473-33-1 | SDF | |
| 化学名 | 3-(4-morpholino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile | ||
| Canonical SMILES | N#CC1=CC=CC(C2=CNC3=NC=NC(N4CCOCC4)=C32)=C1 | ||
| 分子式 | C17H15N5O | 分子量 | 305.33 |
| 溶解度 | ≥ 15.25mg/mL in DMSO | 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 | 3.2751 mL | 16.3757 mL | 32.7514 mL |
| 5 mM | 0.655 mL | 3.2751 mL | 6.5503 mL |
| 10 mM | 0.3275 mL | 1.6376 mL | 3.2751 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。