| CAS NO: | 1062243-51-9 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 543.61 |
|---|---|
| Formula | C27H35F2N7O3 |
| CAS No. | 1062243-51-9 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 100 mg/mL (184.0 mM) |
| Water:<1 mg/mL | |
| Ethanol: 100 mg/mL (184.0 mM) | |
| Other info | InChi Key: DJNZZLZKAXGMMC-UHFFFAOYSA-N InChi Code: InChI=1S/C27H35F2N7O3/c1-34-12-10-18(11-13-34)31-24(37)17-8-9-20(22(14-17)39-3)32-26-30-15-21-23(33-26)36(19-6-4-5-7-19)16-27(28,29)25(38)35(21)2/h8-9,14-15,18-19H,4-7,10-13,16H2,1-3H3,(H,31,37)(H,30,32,33) SMILES Code: O=C(NC1CCN(C)CC1)C2=CC=C(NC3=NC=C(N4C)C(N(C5CCCC5)CC(F)(F)C4=O)=N3)C(OC)=C2 |
| Synonyms | Ro5203280; RO3280; Ro5203280; RO-3280; Ro-5203280; RO 3280; Ro 5203280; 4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide |
| In Vitro | In vitro activity: RO3280 shows the strong anti-proliferative activity against lung cancer cell line H82, colorectal cancer cell HT-29, breast cancer cell MDA-MB-468, prostate cancer cell PC3 and skin cancer cell A375 with IC50s of 5, 10, 19, 12 and 70 nM, respectively. Kinase Assay: Ro3280 is a potent, highly selective inhibitor of PLK1 with an IC50 and a Kd of 3 nM and 0.09 nM, respectively, and nearly has no effect on PLK2 and PLK3. Cell Assay: When tested with a panel of acute leukemia cell lines, Ro3280 showed inhibitory function on U937, HL 60, NB4, K562, MV4-11, and CCRF with IC50 value of 186 nM, 175 nM, 74 nM, 797 nM, 120 nM, and 162 nM, respectively. It was interesting to notice that ALL cells (35.49-110.76 nM) were more sensitive to Ro3280 compared with AML cells (IC50, 52.80-147.50 nM). Further, it was showed that Ro3280 treatment decreased cell viability, induced apoptosis and disrupted cell cycle [3]. In H82 (lung cancer), HT-29 (colon cancer), MDA-MB-468 (breast cancer), PC3 (prostate cancer), and A375 (cutaneum carcinoma), Ro3280 treatment inhibited PLK1 with the IC50 was 5 nM, 10 nM, 19 nM, 12 nM, and 70 nM, respectively. |
|---|---|
| In Vivo | Nude mice bearing HT-29 xenografts administered with MLN0905 (6.25 mg/Kg - 50 mg/Kg, p.o.) shows dose-dependent pharmacodynamic responses (48 hours after treatment). OCI LY-19-Luc tumor bearing mice administered with MLN0905 (3.12 mg/Kg – 6.25 mg/Kg, p.o.) shows significant pharmacodynamic responses amd peaks at 8 hours after treatment. MLN0905 shows antitumor efficacy in treatment with OCI LY-19-Luc xenografts bearing scid mice for 21 days. The T/C of 6.25 mg/Kg daily group is 0.15. |
| Animal model | RO3280 displays robust antitumor activity in nude mouse implanted with HT-29 human colorectal tumors ranging from 72% tumor growth inhibition when dosed once weekly at 40 mg/kg, to complete tumor regression when dosed more frequently |
| Formulation & Dosage | Mice (female, 4-5 weeks of age) are used in the assay. Cells (5 × 106 cells in 150 μL) are suspended in RPMI 1640 and injected subcutaneously into the flank of each BALB/c nude mouse. On day 5, tumour size is measured, the animals are randomized into two groups (n = 15 per group), and RO3280 (40 mg/kg, once every 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 the resulting tumours (in millimetres) are measured every 3 days with callipers. The tumour diameter is measured, 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 also performed with these sections. Then, the tumours are fixed, embedded and cut into 3‐μm‐ hick sections, which are subsequently stained with haematoxylin and eosin to permit the observation of the tumour margin |
| References | Bioorg Med Chem Lett. 2012 Jan 15;22(2):1247-50. |
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