522629-08-9
522629-08-9 structure
- Name: CGP 57380
- Chemical Name: 3-N-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine
- CAS Number: 522629-08-9
- Molecular Formula: C11H9FN6
- Molecular Weight: 244.228
- Catalog: Signaling Pathways MAPK/ERK Pathway MNK
- Create Date: 2019-02-16 19:39:04
- Modify Date: 2024-01-02 20:36:00
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CGP 57380 is a cell-permeable pyrazolo-pyrimidine compound that acts as a selective inhibitor of Mnk1 with IC50 of 2.2 μM, but has no inhibitory activity against p38, JNK1, ERK1/2, PKC, or Src-like kinases.
| Name | 3-N-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine |
|---|---|
| Synonyms |
1H-Pyrazolo[3,4-d]pyrimidine-3,4-diamine, N-(4-fluorophenyl)-
N-(4-Fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-3,4-diamine CGP57380 N3-(4-fluorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine CGP-57380 CGP 57380 |
| Description | CGP 57380 is a cell-permeable pyrazolo-pyrimidine compound that acts as a selective inhibitor of Mnk1 with IC50 of 2.2 μM, but has no inhibitory activity against p38, JNK1, ERK1/2, PKC, or Src-like kinases. |
|---|---|
| Related Catalog | |
| Target |
MNK1:2.2 μM (IC50) |
| In Vitro | CGP57380 inhibits phosphorylation of eIF4E in cellular assays with IC50 of about 3 μM. CGP57380 causes dephosphorylation of eIF4E, and induces a further increase in the cap-dependent reporter in 293 cells[1]. CGP57380 results in dose-dependent decreases in Ang II-stimulated phosphorylation of eIF4E, protein synthesis, and VSMC hypertrophy[2]. CGP57380 sensitizes wild-type cells for serum-withdrawal induced apoptosis in mouse embryo fibroblasts (MEFs)[3]. CGP57380 prevents the serial replating function of BC progenitors[4]. |
| In Vivo | CGP57380 (40 mg/kg/d i.p.) potently extinguishes the ability of BC CML cells to serially transplant-immunodeficient mice and function as LSCs[4]. |
| Kinase Assay | Recombinant p38 isoforms are activated by Mkk6(E) under the following conditions: p38 (100 ng/mL), Mkk6(E) (30 ng/mL), ATP (100 mM) are mixed in kinase buffer (25 mM Hepes, 25 mM b-glycerophosphate, 0.1 mM sodium orthovanadate, 25 mM MgCl2, 2.5 mM DTT, pH 7.4) and incubated for 30 min at 30°C. A typical assay reaction for Mnk1 activity contained Mnk1 (2 ng/mL), HA-eIF4E (10 ng/mL), ATP (300 mM) in kinase buffer. The reaction is started by addition of activated p38 (0.03-3 ng/mL) and stopped after 30 min at 30°C by addition of SDS loading buffer. Inhibitors of Mnk1 are identified under the same assay conditions, except that Mnk1 is pre-activated using active p38a before exposure to the substrate and inhibitors. |
| Animal Admin | CD34+ cells (5×105) or GMPs (1×105) are resuspended in 25 μL 1% FBS/PBS solution and injected into the right femur of 8- to 10-wk-old sublethally irradiated (200 cGy) female mice (n=5 mice per group). Mice injected with 1% FBS/PBS solution serve as a sham control for each experiment. Beginning at 4 wk posttransplantation, mice are monitored for engraftment of human cells by flow cytometry. At 6 wk after transplantation, engrafted mice are treated with vehicle alone, dasatinib (5 mg/kg/d) by gavage, or CGP57380 (40 mg/kg/d) intraperitoneally for 3 wk (n=5 mice per group). At the end of treatment, mice are euthanized, and CD45+ cells are isolated from BM and spleen by using anti-human CD45-specific immunomagnetic microbeads. An aliquot of 1×105 human CD45+ cells is seeded into methylcellulose for the colony forming cell (CFC) assay, and colonies are enumerated after 2 wk. All of the remaining human cells from each primary transplant recipient are then transplanted by intrafemoral injection into secondary recipients, and human engraftment is monitored at 2-wk intervals beginning at 4 wk. At the end of 16 wk, all mice are euthanized. Engraftment in BM and blood is assessed by flow cytometry, and BCR-ABL1 transcripts are detected by RT-PCR. |
| References |
| Density | 1.6±0.1 g/cm3 |
|---|---|
| Boiling Point | 541.6±50.0 °C at 760 mmHg |
| Molecular Formula | C11H9FN6 |
| Molecular Weight | 244.228 |
| Flash Point | 281.4±30.1 °C |
| Exact Mass | 244.087280 |
| PSA | 92.51000 |
| LogP | 1.28 |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.809 |
| Storage condition | -20℃ |
| Symbol |
GHS07 |
|---|---|
| Signal Word | Warning |
| Hazard Statements | H319 |
| Precautionary Statements | P305 + P351 + P338 |
| Personal Protective Equipment | Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter |
| RIDADR | NONH for all modes of transport |