CAS 522629-08-9|CGP 57380
| Common Name | CGP 57380 | ||
|---|---|---|---|
| CAS Number | 522629-08-9 | Molecular Weight | 244.228 |
| Density | 1.6±0.1 g/cm3 | Boiling Point | 541.6±50.0 °C at 760 mmHg |
| Molecular Formula | C11H9FN6 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | 281.4±30.1 °C |
| Symbol | GHS07 | Signal Word | Warning |
Names
| Name | 3-N-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine |
|---|---|
| Synonym | More Synonyms |
CGP 57380 BiologicalActivity
| 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 | Signaling Pathways >>MAPK/ERK Pathway >>MNKResearch Areas >>Cancer |
| 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 | [1]. Knauf U, et al. Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol. 2001 Aug;21(16):5500-11. [2]. Ishida M, et al. Mnk1 is required for angiotensin II-induced protein synthesis in vascular smooth muscle cells. Circ Res. 2003 Dec 12;93(12):1218-24. Epub 2003 Nov 6 [3]. Chrestensen CA, et al. Loss of MNK function sensitizes fibroblasts to serum-withdrawal induced apoptosis. Genes Cells. 2007 Oct;12(10):1133-40. [4]. Lim S, et al. Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):E2298-307 |
Chemical & Physical Properties
| 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 |
| InChIKey | UQPMANVRZYYQMD-UHFFFAOYSA-N |
| SMILES | Nc1ncnc2n[nH]c(Nc3ccc(F)cc3)c12 |
| Storage condition | -20℃ |
Safety Information
| 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 |
Articles9
More Articles| Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget 5(17) , 7691-704, (2014) Dysregulation of cellular transcription and translation is a fundamental hallmark of cancer. As CDK9 and Mnks play pivotal roles in the regulation of RNA transcription and protein synthesis, respectiv... | |
| MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL. Nat. Commun. 5 , 5413, (2014) The phosphorylation of eIF4E1 at serine 209 by MNK1 or MNK2 has been shown to initiate oncogenic mRNA translation, a process that favours cancer development and maintenance. Here, we interrogate the M... | |
| Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells. Cancer Lett. 357(2) , 612-23, (2015) The Ras/Raf/MAPK and PI3K/Akt/mTORC1 cascades are two most aberrantly regulated pathways in cancers. As MAPK-interacting kinases (Mnks) are part of the convergent node of these two pathways, and play ... |
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 |
