| CAS |
No.1086062-66-9 |
| 英文名称 |
Omipalisib |
| 别名 |
;GSK2126458;GSK-2126458;Omipalisib;deltisonab;betanisona;methylprednisone |
| 分子式 |
C25H17F2N5O3S |
| 分子量 |
505.5 |
| 溶解性 |
Soluble in DMSO(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD16038929 |
| SMILES |
COC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C4=CN=NC=C4)NS(=O)(=O)C5=C(C=C(C=C5)F)F |
| InChIKey |
CGBJSGAELGCMKE-UHFFFAOYSA-N |
| InChI |
InChI=1S/C25H17F2N5O3S/c1-35-25-23(32-36(33，34)24-5-3-18(26)12-21(24)27)11-17(13-29-25)15-2-4-22-20(10-15)19(7-8-28-22)16-6-9-30-31-14-16/h2-14，32H，1H3 |
| PubChem CID |
25167777 |
| 靶点 |
PI3K |
| 通路 |
PI3K/Akt/mTOR |
| 背景说明 |
是一种有效的，高选择性的 PI3K 抑制剂，具有抗癌活性。 |
| 生物活性 |
Omipalisib (GSK2126458) is an orally active and highly selective inhibitor of PI3K with Kis of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ， mTORC1/2， respectively. Omipalisib has anti-cancer activity.[1-3] |
| In Vitro |
Omipalisib (GSK2126458) 有效抑制人类癌症中常见的 p110α 激活突变体 (E542K、E545K 和 H1047R) 的活性，Ki 分别为 8 pM、8 pM 和 9 pM。Omipalisib 显著降低 pAkt-S473 的水平，在 T47D 和 BT474 细胞中具有显著的效力，IC50 分别为 0.41 nM 和 0.18 nM。此外，Omipalisib (GSK2126458) 导致 G1 细胞周期停滞，并对大量细胞系的细胞增殖产生抑制作用，包括 T47D 和 BT474 乳腺癌细胞系，IC50 分别为 3 nM，2.4 nM[1]。Omipalisib 或 GSK1120212 与 Omipalisib 的组合增强细胞生长抑制并降低 A375 BRAF (V600E) 和 YUSIT1 BRAF (V600K) 黑色素瘤细胞系的耐药克隆中的 S6 核糖体蛋白磷酸化[2]。Omipalisib (GSK2126458) 增强结直肠癌细胞系中 DDR1-IN-1 的抗增殖活性[3]。 |
| In Vivo |
在 BT474 人肿瘤异种移植模型中，Omipalisib (GSK2126458) 处理导致 pAkt-S473 水平呈剂量依赖性降低，并在 300 μg/kg 的低剂量下表现出剂量依赖性肿瘤生长抑制。此外，Omipalisib (GSK2126458) 在四种临床前动物 (小鼠、大鼠、狗和猴) 中表现出低血液清除率和良好的口服生物利用度[1]。 |
| 细胞实验 |
BT474， HCC1954 and T-47D (human breast) are cultured in RPMI-1640 containing 10% fetal bovine serum at 37°C in 5% CO2 incubator. Cells are split into T75 flask two to three days prior to assay set up at density which yields approximately 70-80% confluence at time of harvest for assay. Cells are harvested using 0.25% trypsin-EDTA. Cell counts are performed on cell suspension using Trypan Blue exclusion staining. Cells are then plated in 384 well black flat bottom polystyrene in 48 μL of culture media per well at 1，000 cells/well. All plates are placed at 5% CO2， 37°C overnight and Omipalisib (GSK2126458) is added the following day. One plate is treated with CellTiter-Glo for a day 0 (t=0) measurement and read as described below. Omipalisib (GSK2126458) is prepared in clear bottom polypropylene 384 well plates with consecutive two fold dilutions. 4 μL of these dilutions are added to 105 μL culture media， after mixing the solution， 2 μL of these dilutions are added into each well of the cell plates. The final concentration of DMSO in all wells is 0.15%. Cells are incubated at 37°C， 5% CO2 for 72 hours. Following 72 hours of incubation with Omipalisib each plate is developed and read. CellTiter-Glo reagent is added to assay plates using a volume equivalent to the cell culture volume in the wells. Plates are shaken for approximately two minutes and incubated at room temperature for approximately 30 minutes and chemiluminescent signal is read on the Analyst GT reader. Results are expressed as a percent of the t=0 and plotted against the Omipalisib (GSK2126458) concentration. Cell growth inhibition is determined for Omipalisib (GSK2126458) by fitting the dose response with a 4 or 6 parameter curve fit using XLfit software and determining the concentration that inhibits 50% of the cell growth (gIC50) with the Y min as the t=0 and Y max as the DMSO control. Value from wells with no cells is subtracted from all samples for background correction.. |
| 数据来源文献 |
[1]. Knight SD， et al. Discovery of GSK2126458， a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Med. Chem. Lett. 2010， 1 (1)， 39-43.
[2]. Greger JG， et al. Combinations of BRAF， MEK， and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib， mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012 Apr;11(4):909-20.
[3]. Kim HG， et al. Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol. 2013 Oct 18;8(10):2145-50. |
| 规格 |
1mg 5mg 10mg 50mg |
| 单位 |
瓶 |
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英语
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