FN-1501 - CDK 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFN-1501Cat. No.: HY-111361CAS No.: 1429515-59-2分式: CHNO分量: 431.49作靶點(diǎn): CDK; FLT3作通路: Cell Cycle/DNA Damage; Protein Tyrosine Kinase/RTK儲(chǔ)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(shí)驗(yàn) DMSO : 50 mg/m

2、L (115.88 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3176 mL 11.5878 mL 23.1755 mL5 mM 0.4635 mL 2.3176 mL 4.6351 mL10 mM 0.2318 mL 1.1588 mL 2.3176 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 FN-1501種有效的 FLT3 和 CDK 抑制劑，對(duì)

3、CDK2/cyclin A，CDK4/cyclin D1，CDK6/cyclin D1 和 FLT3 的IC50 值分別為 2.47，0.85，1.96, 和 0.28 nM。FN-1501 具有抗腫瘤的活性。IC50 & Target Cdk4/cyclin D1 CDK6/cyclinD1 cdk2/cyclin A FLT30.85 nM (IC50) 1.96 nM (IC50) 2.47 nM (IC50) 0.28 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 FN-1501 is a potent i

4、nhibitor of FLT3 and CDK, with IC50s of 2.47 0.21, 0.85 0.28, 1.96 0.08 and 0.28 0.01 nM for CDK2/cyclin A, CDK4/cyclin D1, CDK6/cyclin D1 and FLT3, respectively. FN-1501 shows potentinhibitory activity against several tumor cells, such as MGC803, RS4;11, MCF-7, HCT-116, and NCI-H82,with GI50s of 0.

5、37 0.04, 0.05 0.01, 2.84 0.25, 0.09 0.04, 0.11 0.02 nM, respectively 1.體內(nèi)研究 FN-1501 exhibits potent antitumor activity, and shows little cytotoxicity on normal lymphocyte cells, with LD50of 185.67 mg/kg in ICR mice. FN-1501 (15. 30, or 40 mg/kg/d, i.v.) dose-dependently and significantlysuppresses t

6、he growth of tumor in MV4-11-cell-inoculated-xenograft mice 1.PROTOCOLKinase Assay 1 The activity of the CDKs and FLT3 are assayed in reaction buffer (20 mM HEPES pH 7.5, 10 mM MgCl2, 1mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO) at room temperature ata final ATP concentr

7、ation of 10 mM. Then FLT3, dissolved in 100% DMSO at the indicated doses, aredelivered into the kinase reaction mixture by acoustic technology and incubated for 20 min at roomtemperature. After 10 M -33P ATP (specific activity 10 Ci/L) is added to initiate the reaction, thereactions are carried out

8、at 25C for 120 min. The kinase activities are detected by the filterbinding method.IC50 values and curve fits are obtained by Prism 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 The human AML cell line MV4-11 is cultured in IMDM media w

9、ith 10% FBS and supplemented with 2% l-glutamine and 1% penicillin/streptomycin. The MV4-11 cell line is maintained in culture media at 37C with5% CO2. The effects of FN-1501 on MV4-11 proliferation are performed. Cells are cultured in 96-well cultureplates (10000 cells/well). FN-1501 at various con

10、centrations is added to the plates. Cell proliferation isdetermined after treatment with FN-1501 for 72 h. Cell viability is measured using the CellTiter-Glo assay,and luminescence is measured in a multilabel reader. Data are normalized to control groups (DMSO) andrepresented as the means of three i

11、ndependent measurements with standard errors of 50 values arecalculated using Prism 5.0 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Six-week-old female nu/nu mice are housed in a specific pathogen-free facility. Prior

12、 to implantation, cells areharvested during exponential growth. Five million MV4-11 cells in PBS are formulated as a 1:1 mixture with aMatrigel and injected into the subcutaneous space on the right flank of each nu/nu mouse. Daily intravenousinjections are initiated when MV4-11 tumors have reached s

13、izes of 100-200 mm3. The animals are thenrandomized into treatment groups of 8 mice each for the efficacy studies and dosed with FN-1501 (0, 15, 30,or 40 (mg/kg)/d) or cytarabine (50 (mg/kg)/d). The compounds (FN-1501, etc.) are dissolved in a solution ofPEG400 (25%), ethanol (3.7%), glucose (5%), a

14、nd acetic acid/sodium acetate buffer (pH 4.5, 7.5%). Tumorgrowth is measured every 3 days using Vernier calipers for the duration of the treatment. The volume iscalculated as follows: tumor volume = a b2/2, where a is the long diameter, and b is the short diameter.The percentage of tumor-growth inhi

15、bition (GI) is calculated as follows: GI = 100% 1 - (tumor volumefinal -tumor volumeinitial for the compound-treated group)/(tumor volumefinal - tumor volumeinitial for the vehicle-treated group). The percent tumor regression (PTR) is calculated as follows: PTR = 100% (tumor2/3 Master of Small Molec

16、ules 您邊的抑制劑師www.MedChemEvolumeinitial - tumor volumefinal)/(tumor volumeinitial) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Wang Y, et al. Discovery of 4-(7H-Pyrrolo2,3-dpyrimidin-4-yl)amino)-N-(4-(4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Le