SMI-16a-PIM1-2-Kinase-Inhibitor-VI-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESMI-16aCat. No.: HY-101947CAS No.: 587852-28-6Synonyms: PIM1/2 Kinase Inhibitor VI分式: CHNOS分量: 263.31作靶點: Pim作通路: JAK/STAT Signaling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 : 150 mg/mL

2、 (569.67 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.7978 mL 18.9890 mL 37.9781 mL5 mM 0.7596 mL 3.7978 mL 7.5956 mL10 mM 0.3798 mL 1.8989 mL 3.7978 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。BIOLOGICAL ACTIVITY物活性 SMI-16a是選擇性的 Pim 激酶抑制劑，對Pim1，P

3、im2 和 PC3 細胞的IC50值分別為0.15，0.02 和48 M。IC50 & Target IC50: 0.15 M (Pim1), 0.02 M (Pim2), 48 M (PC3 cells) 1體外研究SMI-16a has excellent potency for inhibition of both Pim-1 and Pim-2 1. Treatment with Pim-2 short-1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEinterference RNA as well as the Pim inhibit

4、or SMI-16a successfully restores osteoblastogenesis suppressedby all the above inhibitory factors and MM cells. The SMI-16a treatment potentiates BMP-2-mediatedanabolic signaling while suppressing TGF- signaling 2.體內研究 Mice tolerate intraperitoneal dose of SMI-16a is 50 mg/kg daily for 5 days, while

5、 100 mg/kg is overtly toxic.Treatment of the animals with SMI-16a for 5 days per week reduces the growth of tumors by approximately50% and does not cause a loss of body weight. Subchronic dosing with SMI-16a does not affect the levels ofred, white blood cells, including lymphocytes, monocytes, and g

6、ranulocytes, indicating that the compounddoes not have myelosuppressive effects. SMI-16a does not have toxicity toward the liver as the albumin,alkaline phosphatase, and alanine aminotransferase levels are unchanged 1. SMI-16a effectively preventsbone destruction while suppressing MM tumor growth in

7、 MM animal models 2.PROTOCOLKinase Assay 1 Recombinant human Pim-1 (Upstate) is incubated with S6 kinase/Rsk-2 peptide 2 (KKRNRTLTK) as thesubstrate in the presence 100 M of compounds from the screening library, 1 M ATP and 10 mM MgCl2 for1 h. The Kinase-Glo luciferase kit is used to measure residua

8、l ATP levels after the kinase reaction 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Human prostate cancer PC3 cells are seeded in 96-well tissue culture dishes at approximately 10%confluency and allowed to attach and recover for 24 h.

9、Varying concentrations of the test compounds (SMI-16a) are then added to each well, and the plates are incubated for an additional 48 h. The number ofsurviving cells is determined by the MTS assay. The percentage of cells killed is calculated as thepercentage decrease in MTS metabolism compared with

10、 control cultures 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Female Balb/C mice are injected subcutaneously with JC cells suspended in PBS. After palpable tumorAdministration 1 growth, animals are treated five days per week by intrap

11、eritoneal injection of vehicle alone or 50 mg/kg ofSMI-16a.Whole body weights and tumor volume measurements are performed three times per week 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Xia Z, et al. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. 2009 Jan 8;52(1):74-86.2. Hiasa M, et al. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia. 2015Jan;29(1):207-17.McePdfHeightCaution: Prod