Ro3280 _Polo-like Kinase (PLK) 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERo3280Cat. No.: HY-15161CAS No.: 1062243-51-9分式: CHFNO分量: 543.61作靶點(diǎn): Polo-like Kinase (PLK)作通路: Cell Cycle/DNA Damage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 : 6.4 mg/mL (11.77 mM; Nee

2、d ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8396 mL 9.1978 mL 18.3955 mL5 mM 0.3679 mL 1.8396 mL 3.6791 mL10 mM 0.1840 mL 0.9198 mL 1.8396 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 Ro3280種有效的，度選擇性的 PLK1 抑制劑，IC50 和 Kd 值分別為 3 nM 和 0.09 nM，對(duì)

3、PLK2 和 PLK3乎沒作。IC50 & Target PLK1 ALK CAMKK1 CAMKK20.09 nM (Kd) 230 nM (Kd) 1100 nM (Kd) 87 nM (Kd)DAPK1 DAPK3 FER GAK1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE100 nM (Kd) 70 nM (Kd) 53 nM (Kd) 87 nM (Kd)MYLK PTK2 PTK2B RPS6KA6 (KinDom.2)170 nM (Kd) 84 nM (Kd) 130 nM (Kd) 560 nM (Kd)TTK51 nM

4、(Kd)體外研究 Ro3280 (RO3280) inhibits PLK1 activity in NB4 and K562 cells, with an IC50s of 13.45 nM and 301 nM,respectively. RO3280 shows inhibitory activities against the growth of six leukemia cells, with IC50s of 186nM, 175 nM, 74 nM, 797 nM, 120 nM and 162 nM for U937, HL60, NB4, K562, MV4-11 and C

5、CRF cell lines,respectively. RO3280 also suppresses the growth of primary ALL and AML cells, with IC50s of 35.49-110.76nM, and 52.80-147.50 nM, respectively. RO3280 (50 or 100 nM) induces apoptosis and cell cycle disorder inacute leukemia cells 1. Ro3280 shows potent activity in H82, H69, A549 lung

6、cancer cell lines with EC50sof 6 nM, 7 nM and 82 nM. Ro3280 also inhibits several other cancer cell lines, with low concentration 2.RO3280 is cytotoxic to 5637 and T24 human bladder cancer cells, with IC50s of appr 100 nM.體內(nèi)研究 Ro3280 (RO3280, 40 mg/kg, i.v.) inhibits 72% tumor growth in a mouse xeno

7、graft model implanted with HT-29 colorectal cancer cells, and when dosed more frequently, RO3280 completely suppresses the tumorgrowth 2. RO3280 (30 mg/kg, once every 5 days, i.p.) shows significant anti-bladder cancer activities in anude mouse model 3.PROTOCOLCell Assay 1 Leukemia cells or primary

8、leukemia cells (2 104) are seeded in 96-well plates overnight and incubated withDMSO, or increasing concentrations of RO3280 (0.05-120 M) for 24 h. The same volume of DMSO addedto the vehicle treated wells. Each drug concentration is replicated four times. Then, 10 L CCK8 solution isadded to each we

9、ll, incubated at 37C for 2-4 h and the optical density (OD) values are measured at 450 nmusing a scanning multi-well spectrophotometer. Relative survival rate is calculated from the absorbancevalues compared with the control group. The proliferation of cells is calculated as a percentage of the DMSO

10、-treated control wells with 50% inhibitory concentration (IC50) values derived after plotting proliferation valueson a logarithmic curve. The IC50 of PLK1 inhibitor is calculated by Graph Prism software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.

11、Animal Briefly, mice (female, 4-5 weeks of age) are used in the assay. Cells (5 106 cells in 150 L) are suspendedAdministration 3 in RPMI 1640 and injected subcutaneously into the flank of each BALB/c nude mouse. On day 5, tumour sizeis measured, the animals are randomized into two groups (n = 15 pe

12、r group), and RO3280 (40 mg/kg, onceevery 5 days) treatment is initiated by intraperitoneal injection. The control group is treated with vehicle (1.5%DMSO in PBS). The drug (or vehicle) treatment is performed for 40 days. The length and width of theresulting tumours (in millimetres) are measured eve

13、ry 3 days with callipers. The tumour diameter ismeasured, and the volume (length width2 0.52) is calculated. The mice are humanely killed on day 45,and the tumours are dissected and weighed. Western blot and immunohistochemistry assays are alsoperformed with these sections. Then, the tumours are fix

14、ed, embedded and cut into 32/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmthick sections, which are subsequently stained with haem atoxylin and eosin to perm it the observation of the tum ourm argin 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.R

15、EFERENCES1. Wang NN, et al. Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor,induces apoptosis in leukemia cells. Int J Mol Sci. 2015 Jan 7;16(1):1266-92.2. Chen S, et al. Identification of novel, potent and selective inhibitors of Polo-like kinase 1. Bioorg Med Chem Lett. 2012 Jan15;22(2):1247-50.3. Zhang Z, et al. Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis inhuman bladder cancer cells. J