| 名稱 | Ridaforolimus |
| 描述 | Ridaforolimus (AP23573) is a small molecule and non-prodrug analogue of the lipophilic macrolide antibiotic rapamycin with potential antitumor activity. Ridaforolimus binds to and inhibits the mammalian target of rapamycin (mTOR), which may result in cell cycle arrest and, consequently, the inhibition of tumor cell growth and proliferation. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway. |
| 細胞實驗 | Cell lines: Colo205,H1755,H1395,H1666,A549,H157,and H1703 cells. Concentrations: Dissolved in ethanol,final concentrations ~ 1 μM. Method: Cells are seeded at 2-3 ×104/mL,and serial dilutions of Deforolimus are added after 2 hours,for at least three cell doublings (72-120 hours).Deforolimus effects are measured by the CellTiter 96 Aqueous nonradioactive cell proliferation assay and Sulforhodamine B assays. |
| 激酶實驗 | HT-1080 cells are treated with increasing concentrations of Deforolimus (0-100 nM) for 2 hours, prior to harvest. Cellular lysates are extracted in denaturing lysis buffer, resolved on SDS-PAGE and transferred to PVDF membranes. After blocking, membranes are incubated with primary antibodies for 1 hour, followed by appropriate HRPconjugated secondary antibodies for 1 hour at room temperature. Immunoreactive proteins are detected using enhanced chemiluminescence and autoradiography performed by exposure to X-ray film. IC50 is determined by the inhibition of levels of phosphorylated ribosomal protein S6 (p-S6) and 4E-BP1 (p-4E-BP1). |
| 動物實驗 | Animal Models: Male and female athymic NCr-nu mice with xenografts established by subcutaneous implantation of PC-3,A549,HCT-116,MCF7,PANC-1 and SK-LMS-1 tumors. Formulation: Dissolved in ethanol,and diluted in a vehicle of 4% ethanol,5% Tween 80,and 5% propylene glycol. Dosages: ~10 mg/kg. Administration: Intraperitoneally injection |
| 體外活性 | Deforolimus以劑量依賴性方式在攜帶PC-3（前列腺）,HCT-116（結腸）,MCF7（乳房）,PANC-1（胰腺）或A549（肺）異種移植物的小鼠中發(fā)揮顯著的抗腫瘤作用,在與抑制腫瘤生長相關的SK-LMS-1異種移植模型中抑制mTOR信號傳導. |
| 體內活性 | Deforolimus劑量依賴性抑制HT-1080細胞中S6和4E-BP1磷酸化,IC50分別為0.2 nM和5.6 nM,EC50分別為0.2 nM和1.0 nM,且導致細胞尺寸減小,G1期細胞增多,抑制葡萄糖攝取,EC50為0.1-1 nM。Deforolimus作用于一組細胞系,具有顯著抗增殖活性,EC50為0.2-2.3 nM。Deforolimus有效且選擇性及劑量依賴性抑制VEGF產量,EC50為~0.1 nM。Deforolimus和MEK抑制劑CI-1040或 PD0325901聯(lián)用作用于人肺癌細胞系,具有協(xié)同作用,這種作用存在劑量依賴性,這種作用與細胞增殖受抑制而非細胞凋亡增多相關,處理24小時后,抑制40%核糖體合成,且使多核糖體/染色單體比例下降。Deforolimus顯著抑制人NSCLC細胞系（除了H157細胞）細胞生長,IC30為2.45-8.83 nM,而作用于H157細胞時,IC30 >20 nM。2.8-5.9 nM Deforolimus處理A549,H1703和H157細胞（除了表達mTORC1耐藥變異的H1666）,使p70S6KThr389去磷酸化,提高A549和H1703細胞中pAKTser473和pAKTThr308磷酸化水平。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 182 mg/mL (183.8 mM)
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| 關鍵字 | inhibit | Autophagy | MK 8669 | Mammalian target of Rapamycin | mTOR | Ridaforolimus | Inhibitor | MK8669 | AP-23573 | AP 23573 |
| 相關產品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Xylitol | Hydroxychloroquine | Curcumin | Stavudine | Myricetin | Paeonol | Sodium 4-phenylbutyrate |