PF-4618433
目录号 : GC61852
PF-4618433 是一种有效的、选择性的 PYK2 抑制剂，IC50 值为 637 nM。PF-4618433 可能适用于研究骨质疏松症，颅面和阑尾骨骼缺损以及靶向骨再生。
Cas No.:1166393-85-6
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-4618433 is a potent and selective PYK2 inhibitor, with an IC50 of 637 nM. PF-4618433 may be suitable for the research of osteoporosis, craniofacial and appendicular skeletal defects and for targeted bone regeneration[1][2].
PF-4618433 (0.1-1.0 µM; 7 days) promotes osteogenesis of hMSC cultures. PF-4618433 increases in both alkaline phosphatase (ALP) activity and mineralization in a dependent manner[1].PF-4618433 (0.1-0.3 µM; 24 hours) enhances osteoblast proliferation[2].PF-4618433 (0.0125-0.3 µM; 14 or 21 days) enhances calcium deposition at the concentrations of 0.1 and 0.3 µM[2].
References:
[1]. Seungil H, et, al. Structural Characterization of Proline-Rich Tyrosine Kinase 2 (PYK2) Reveals a Unique (DFG-out) Conformation and Enables Inhibitor Design. J Biol Chem. 2009 May 8; 284(19): 13193-201.
[2]. Sumana P, et, al. A Pyk2 Inhibitor Incorporated Into a PEGDA-gelatin Hydrogel Promotes Osteoblast Activity and Mineral Deposition. Biomed Mater. 2019 Feb 27; 14(2): 025015.
| Cas No. | 1166393-85-6 | SDF | |
| Canonical SMILES | O=C(NC1=CC(COC2=CC=CN=C2)=NN1)NC3=CC(C(C)(C)C)=NN3C4=CC=C(C)C=C4 | ||
| 分子式 | C24H27N7O2 | 分子量 | 445.52 |
| 溶解度 | DMSO : 125 mg/mL (280.57 mM) | 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 | 2.2446 mL | 11.2228 mL | 22.4457 mL |
| 5 mM | 0.4489 mL | 2.2446 mL | 4.4891 mL |
| 10 mM | 0.2245 mL | 1.1223 mL | 2.2446 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。
Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design
J Biol Chem 2009 May 8;284(19):13193-201.PMID:19244237DOI:PMC2676051
Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibitor, PF-431396, within the FAK family is explained by our structural analyses. Importantly, the novel DFG-out conformation with two diarylurea inhibitors (BIRB796, PF-4618433) reveals a distinct subclass of non-receptor tyrosine kinases identifiable by the gatekeeper Met-502 and the unique hinge loop conformation of Leu-504. This is the first example of a leucine residue in the hinge loop that blocks the ATP binding site in the DFG-out conformation. Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors.