CGP-57380 - MNK 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECGP 57380Cat. No.: HY-10520CAS No.: 522629-08-9分式: CHFN分量: 244.23作靶點: MNK作通路: MAPK/ERK Pathway儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 6 mg/mL (24.57 mM; Need ultrasonic and warming)

2、Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 4.0945 mL 20.4725 mL 40.9450 mL5 mM 0.8189 mL 4.0945 mL 8.1890 mL10 mM 0.4095 mL 2.0473 mL 4.0945 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑

3、前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (10.24 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (10.24 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 CGP

4、57380種細胞滲透的吡唑-嘧啶類化合物，為具有選擇性的 Mnk1 抑制劑，IC50 值為 2.2 M，但是對 p38，JNK1，ERK1/2，PKC 或 Src-like 激酶等沒有抑制作。IC50 & Target MNK12.2 M (IC50)體外研究 CGP57380 inhibits phosphorylation of eIF4E in cellular assays with IC50 of about 3 M. CGP57380 causesdephosphorylation of eIF4E, and induces a further increase in the ca

5、p-dependent reporter in 293 cells 1.CGP57380 results in dose-dependent decreases in Ang II-stimulated phosphorylation of eIF4E, proteinsynthesis, and VSMC hypertrophy 2. CGP57380 sensitizes wild-type cells for serum-withdrawal inducedapoptosis in mouse embryo fibroblasts (MEFs) 3. CGP57380 prevents

6、the serial replating function of BCprogenitors 4.體內(nèi)研究 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.PROTOCOLKinase Assay 1 Recombinant p38 isoforms are activated by Mkk6(E) under the following condition

7、s: 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 30C. Atypical assay reaction for Mnk1 activity contained Mnk1 (2 ng/mL), HA-eIF4E (10 ng/mL)

8、, ATP (300 mM) inkinase buffer. The reaction is started by addition of activated p38 (0.03-3 ng/mL) and stopped after 30 min at30C 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

9、to the substrate and inhibitors.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal CD34+ cells (5105) or GMPs (1105) are resuspended in 25 L 1% FBS/PBS solution and injected into theAdministration 4 right femur of 8- to 10-wk-old sublethally irradia

10、ted (200 cGy) female mice (n=5 mice per group). Miceinjected with 1% FBS/PBS solution serve as a sham control for each experiment. Beginning at 4 wkposttransplantation, mice are monitored for engraftment of human cells by flow cytometry. At 6 wk aftertransplantation, engrafted mice are treated with

11、vehicle alone, dasatinib (5 mg/kg/d) by gavage, orCGP57380 (40 mg/kg/d) intraperitoneally for 3 wk (n=5 mice per group). At the end of treatment, mice areeuthanized, and CD45+ cells are isolated from BM and spleen by using anti-human CD45-specificimmunomagnetic microbeads. An aliquot of 1105 human C

12、D45+ cells is seeded into methylcellulose for thecolony forming cell (CFC) assay, and colonies are enumerated after 2 wk. All of the remaining human cellsfrom each primary transplant recipient are then transplanted by intrafemoral injection into secondaryrecipients, and human engraftment is monitore

13、d at 2-wk intervals beginning at 4 wk. At the end of 16 wk, allmice are euthanized. Engraftment in BM and blood is assessed by flow cytometry, and BCR-ABL1 transcriptsare detected by RT-PCR.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of S

14、mall Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Viruses. 2018 Nov 1;10(11). pii: E601. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Knauf U, et al. Negative regulation of protein translation by mitogen-activated protein kinase-interacting ki

15、nases 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 Dec12;93(12):1218-24. Epub 2003 Nov 63. Chrestensen CA, et al. Loss of MNK function sensitizes fibroblasts to serum-withdrawal induced apoptosis. Genes Cells. 2007Oct;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 NatlAcad Sci U