CGP-57380

CGP-57380 is a selective inhibitor of MAP kinase-interacting kinase 1 (MNK1) in vitro (IC50 = 2.2 μM). MNK1 overexpression was confirmed in both primary GBMs and glioma cell lines. Inhibition of MNK1 activity in GBM cells by the small molecule CGP-57380 suppressed eIF4E phosphorylation, proliferation, and colony formation whereas concomitant treatment with CGP-57380 and the mTOR inhibitor rapamycin accentuated growth inhibition and cell-cycle arrest.

Product information

CAS Number: 522629-08-9

Molecular Weight: 244.23

Formula: C11H9FN6

Synonym:

CGP 57380

CGP57380

CGP-57380

Chemical Name: N3-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-3,4-diamine

Smiles: NC1N=CN=C2NN=C(NC3C=CC(F)=CC=3)C2=1

InChiKey: UQPMANVRZYYQMD-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

CGP-57380 inhibits phosphorylation of eIF4E in cellular assays with IC50 of about 3 μM. CGP-57380 causes dephosphorylation of eIF4E, and induces a further increase in the cap-dependent reporter in 293 cells. CGP-57380 results in dose-dependent decreases in Ang II-stimulated phosphorylation of eIF4E, protein synthesis, and VSMC hypertrophy. CGP-57380 sensitizes wild-type cells for serum-withdrawal induced apoptosis in mouse embryo fibroblasts (MEFs). CGP-57380 prevents the serial replating function of BC progenitors.

In Vivo:

CGP-57380 (40 mg/kg/d i.p.) potently extinguishes the ability of BC CML cells to serially transplant-immunodeficient mice and function as LSCs.

References:

1. Grzmil M, Huber RM, Hess D, Frank S, Hynx D, Moncayo G, Klein D, Merlo A, Hemmings BA. MNK1 pathway activity maintains protein synthesis in rapalog-treated gliomas. J Clin Invest. 2014 Feb;124(2):742-54. doi: 10.1172/JCI70198. Epub 2014 Jan 9. PubMed PMID: 24401275; PubMed Central PMCID: PMC3904612.
2. Dumoulin MC, Aton SJ, Watson AJ, Renouard L, Coleman T, Frank MG. Extracellular signal-regulated kinase (ERK) activity during sleep consolidates cortical plasticity in vivo. Cereb Cortex. 2015 Feb;25(2):507-15. doi: 10.1093/cercor/bht250. Epub 2013 Sep 17. PubMed PMID: 24047601; PubMed Central PMCID: PMC4303804.
3. Diab S, Teo T, Kumarasiri M, Li P, Yu M, Lam F, Basnet SK, Sykes MJ, Albrecht H, Milne R, Wang S. Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as potent Mnk2 inhibitors: synthesis, SAR analysis and biological evaluation. ChemMedChem. 2014 May;9(5):962-72. doi: 10.1002/cmdc.201300552. Epub 2014 Feb 12. PubMed PMID: 24677692.

Products are for research use only. Not for human use.