TP-3654 - Pim 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETP-3654Cat. No.: HY-101126CAS No.: 1361951-15-6分式: CHFNO分量: 418.46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 : 50 mg/mL (119.49 mM; Need ultrasonic)H2O : 4

2、0% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.97 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.97 mM); Precipitated solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.0

3、8 mg/mL (4.97 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TP-3654第代Pim激酶抑制劑，對Pim-1和Pim-3的Ki值分別為5和42 nM。IC50 & Target Ki: 5 nm(Pim-1), 239 nM (Pim-2), 42 nM (Pim-3) 1體外研究 TP-3654 demonstrates potent PIM-1 specific cellular activity in the PIM-1/BAD overexpression system withan average EC50 of 67 nM. TP

4、-3654 treatment reduces levels of phospho-BAD in vitro using the bladdercancer cell line UM-UC-3. TP-3654 reduces colony growth of T24 and UM-UC3 cells, confirming the PIM-1dependent growth for both cell lines 1.體內(nèi)研究 Oral dosing of 200 mg/kg TP-3654 significantly reduces both UM-UC-3 and PC-3 tumor

5、growth measured byvolume (caliper) and by final tumor weight, with no significant changes in body weight or gross adversetoxicity 1.PROTOCOLCell Assay 1 1 M TP-3654 is tested against 336 kinases at a concentration of 10 M ATP. IC50 determinations ofphosphoinositide 3-kinase (PI3K) (, , , and ) and a

6、ll kinases inhibited by 50% from the initial screen areperformed using 10-dose, three-fold serial dilutions of TP-3654 starting with 10 M at Km ATP concentrationsfor each kinase 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal When tumors of mic

7、e reaches 100 to 200 mm3 by caliper measurement, mice are randomized, and oralAdministration 1 dosing of TP-3654 or vehicle control began and continued every day for 5 days with 2 days off for 18 to 21days. Tumor volumes and body weights were determined twice a week 1.MCE has not independently confi

8、rmed the accuracy of these methods. They are for reference only.REFERENCES1. Foulks JM, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014May;16(5):403-12.McePdfHeightCaution: Product has not been fully validated for medical applications.For