1819363-80-8
1819363-80-8 structure
- Name: PFI-3
- Chemical Name: PFI-3
- CAS Number: 1819363-80-8
- Molecular Formula: C19H19N3O2
- Molecular Weight: 321.373
- Catalog: Biochemical Inhibitor Epigenetics Epigenetic Reader Domain Inhibitor
- Create Date: 2018-02-06 08:30:53
- Modify Date: 2024-01-08 21:39:34
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PFI-3 is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a Kd of 89 nM.
| Name | PFI-3 |
|---|---|
| Synonyms |
2-Propen-1-one, 1-(2-hydroxyphenyl)-3-[(1R,4R)-5-(2-pyridinyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-, (2E)-
(2E)-1-(2-Hydroxyphenyl)-3-[(1R,4R)-5-(2-pyridinyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-2-propen-1-one PFI3 |
| Description | PFI-3 is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a Kd of 89 nM. |
|---|---|
| Related Catalog | |
| Target |
Kd: 89 nM (SMARCA2/4)[1] |
| In Vitro | PFI-3 is a potent, cell-permeable probe capable of displacing ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin. PFI-3 binds avidly to both SMARCA2 and SMARCA4 bromodomains (BROMOScan Kd's between 55 and 110 nM) consistent with the binding constant (Kd=89 nM) measured by isothermal titration calorimetry. PFI-3 does not phenocopy the growth inhibitory effects of SMARCA2 knockdown in lung cancer[1]. Exposure of embryonic stem cells to PFI-3 leads to deprivation of stemness and deregulates lineage specification. Furthermore, differentiation of trophoblast stem cells in the presence of PFI-3 is markedly enhanced[2]. PFI-3 binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII is achieved through a novel bromodomain binding mode of a phenolic headgroup that leads to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date[3]. |
| Kinase Assay | To establish whether PFI-3 intercalates DNA, the compound is assessed using a DNA unwinding assay. PFI-3 (1, 5, or 10 μM), cisplatin, or doxorubicin is incubated with supercoiled pBR322, in the presence of wheat germ topoisomerase I, for 30 min at 37°C. DNA incubated with DMSO in the presence or absence of the enzyme is run as control. After extraction by butanol and chloroform/isoamyl alcohol 24:1, the DNA is run in a 1% (w/v) agarose gel with a 1-kb DNA ladder for 4 hours at 80 V. The gel is then stained with SYBR Safe for 30 min before ultraviolet visualization[2]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 528.5±50.0 °C at 760 mmHg |
| Molecular Formula | C19H19N3O2 |
| Molecular Weight | 321.373 |
| Flash Point | 273.4±30.1 °C |
| Exact Mass | 321.147736 |
| LogP | 2.19 |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.712 |
| Storage condition | 2-8°C |