PFI-2
(Synonyms: (R)-PFI-2) 目录号 : GC17956
PFI-2 ((R)-PFI-2 hydrochloride) hydrochloride 是一种有效的选择性 SET 结构域，含有赖氨酸甲基转移酶 7 (SETD7) 抑制剂。
Cas No.:1627676-59-8
Sample solution is provided at 25 µL, 10mM.
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PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase with IC50 value of 2.0 nM [1].
SET domain containing (lysine methyltransferase) 7 (SETD7) is a protein lysine methyltransferase that acts as monomethyltransferase of lysine 4 on histone H3 (H3K4) and regulates DNA methyltransferase 1 (DNMT1) [1].
PFI-2 is a potent and selective SETD7 methyltransferase inhibitor. (R)-PFI-2 inhibited human SETD7 methyltransferase activity with IC50 value of 2.0 nM. However, (S)-PFI-2 was 500-fold less active with IC50 value of only 1.0 µM. (R)-PFI-2 potently inhibited SETD7 with Morrison Kiapp value of 0.33 nM. (R)-PFI-2 occupied the peptide binding groove and effectively inhibited the binding of SETD7 substrates. In the presence of 20 μM SAM, (R)-PFI-2 bound to SETD7 with KD value of 4.2 nM in a SAM-dependent way. In HEK293 cells, (R)-PFI-2 (10 µM) bound to and stabilized SETD7. In Setd7+/+ murine embryonic fibroblasts (MEFs), (R)-PFI-2 increased nuclear localization of Yes-associated protein (YAP) and the expression of YAP target genes Ctgf, Gli2 and Cdc20 [1].
Reference:
[1]. Barsyte-Lovejoy D, Li F, Oudhoff MJ, et al. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A, 2014, 111(35): 12853-12858.
| Kinase experiment [1]: | |
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Methyltransferase activity |
Recombinant human SETD7 (residues 1–366) and SET domain only (residues109–366) were expressed in Escherichia coli and purified to homogeneity. Methyltransferase activity of SETD7(1-366) was assayed using a scintillation proximity assay monitoring the incorporation of the tritium-labeled methyl group of 3H-SAM into a peptide substrate corresponding to histone H3 residues 1-25 at 2 μM SAM and 2 μM H3(1–25) and 2 nM enzyme. |
| Cell experiment [1]: | |
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Cell lines |
MEFs and MCF7 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0-10 μM, 2h |
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Applications |
In Setd7+/+ murine embryonic fibroblasts (MEFs) in the presence of (R)-PFI-2 (10 μM), Setd7+/+ MEFs grown to confluence and displayed increased nuclear localization of YAP, as well as increased expression of YAP-dependent genes Ctgf, Gli2, and Cdc20. (R)-PFI-2 had no effect in Setd7-/- MEFs. In confluent MCF7 cells, (R)-PFI-2 (1 μM for 2h) dose-dependently increased nuclear YAP and increased expression of the YAP target genes AREG and CYR61. |
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References: [1]. Barsyte-Lovejoy D, Li F, Oudhoff MJ, et al. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A, 2014, 111(35): 12853-12858. | |
| Cas No. | 1627676-59-8 | SDF | |
| 别名 | (R)-PFI-2 | ||
| 化学名 | 8-fluoro-N-[(2R)-1-oxo-1-pyrrolidin-1-yl-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide | ||
| Canonical SMILES | C1CCN(C1)C(=O)C(CC2=CC(=CC=C2)C(F)(F)F)NS(=O)(=O)C3=CC(=C4CNCCC4=C3)F | ||
| 分子式 | C23H25F4N3O3S | 分子量 | 499.52 |
| 溶解度 | ≥ 50mg/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 | 2.0019 mL | 10.0096 mL | 20.0192 mL |
| 5 mM | 0.4004 mL | 2.0019 mL | 4.0038 mL |
| 10 mM | 0.2002 mL | 1.001 mL | 2.0019 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet