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Purity: ≥98%
CGP57380 (CGP-57380) is a potent, cell-permeable and selcetive MNK1 inhibitor with anticancer activity. With an IC50 of 2.2 μM, it blocks MNK1 but has no inhibitory effect on p38, JNK1, ERK1 and -2, PKC, or c-Src-like kinases. CGP 57380 (10 μM) prevented the phosphorylation of eIF4E in 293 cells in response to fetal calf serum (FCS), arsenite, anisomycin, PMA, or tumor necrosis factor-alpha. The cap-dependent reporter rluc was also boosted by CGP 57380. CGP 57380 had an IC50 value of 3 μM when used in cellular assays to inhibit the phosphorylation of eIF4E. CGP 57380 decreased protein synthesis, angiotensin II-induced VSMC hypertrophy, and eIF4E phosphorylation in rat vascular smooth muscle cells in a dose-dependent manner.
| Targets |
MNK1 (IC50 = 2.2 μM)
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| ln Vitro |
CGP57380 inhibits phosphorylation of eIF4E in cellular assays with IC50 of about 3 μM. Dephosphorylating eIF4E with CGP57380 results in 293 cells expressing more of the cap-dependent reporter.[1] CGP57380 inhibits protein synthesis, VSMC hypertrophy, and Ang II-stimulated eIF4E phosphorylation in a dose-dependent manner.[2] In mouse embryo fibroblasts (MEFs), CGP57380 makes wild-type cells more susceptible to the apoptosis that is caused by serum withdrawal.[3] CGP57380 stops BC progenitors from repeatedly replicating.[4]
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| ln Vivo |
CGP57380 (40 mg/kg/d i.p.) potently extinguishes BC CML cells' capacity to function as LSCs and serially transplant immunodeficient mice. [4]
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| Enzyme Assay |
CGP 57380 is potent inhibitor of MNK1 with IC50 value of 2.2 μM.
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| Cell 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. Mnk1 (2 ng/mL), HA-eIF4E (10 ng/mL), and ATP (300 mM) were the main components of a typical assay reaction for Mnk1 activity. Addition of activated p38 (0.03–3 ng/mL) initiates the reaction, which is terminated by the addition of SDS loading buffer 30 minutes later at 30°C. The same assay conditions are used to identify Mnk1 inhibitors, but Mnk1 is first preactivated using active p38a before being exposed to the substrate and inhibitors.
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| Animal Protocol |
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). For each experiment, 1% FBS/PBS solution-injected mice serve as the sham control. Using flow cytometry, mice are examined every 4 weeks after the transplant to see if human cells have grafted. Engrafted mice are treated for 3 weeks with CGP57380 (40 mg/kg/d) intraperitoneally, dasatinib (5 mg/kg/d) by gavage, or vehicle alone (n = 5 mice per group) after 6 weeks following transplantation. After the course of treatment is complete, mice are put down, and CD45+ cells are extracted from the BM and spleen using anti-human CD45-specific immunomagnetic microbeads. In the colony forming cell (CFC) assay, an aliquot of 1×105 human CD45+ cells is seeded into methylcellulose, and colonies are counted after 2 weeks. The remaining human cells from each primary transplant recipient are then all intrafemorally injected into secondary recipients, and human engraftment is monitored every two weeks starting at four weeks. All mice are put to death after 16 weeks. RT-PCR is used to find BCR-ABL1 transcripts, and flow cytometry is used to evaluate engraftment in BM and blood.
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| References |
| Molecular Formula |
C11H9FN6
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| Molecular Weight |
244.23
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| Exact Mass |
244.09
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| Elemental Analysis |
C, 54.10; H, 3.71; F, 7.78; N, 34.41
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| CAS # |
522629-08-9
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1=CC(=CC=C1NC2=C3C(=NC=NC3=NN2)N)F
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| InChi Key |
UQPMANVRZYYQMD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H9FN6/c12-6-1-3-7(4-2-6)16-11-8-9(13)14-5-15-10(8)17-18-11/h1-5H,(H4,13,14,15,16,17,18)
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| Chemical Name |
3-N-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidine-3,4-diamine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 4% DMSO +30%PEG 300 +ddH2O: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0945 mL | 20.4725 mL | 40.9450 mL | |
| 5 mM | 0.8189 mL | 4.0945 mL | 8.1890 mL | |
| 10 mM | 0.4095 mL | 2.0473 mL | 4.0945 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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