| 名稱(chēng) | 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(xì)胞實(shí)驗(yàn) | 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(shí)驗(yàn) | 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(dòng)物實(shí)驗(yàn) | 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(lài)性方式在攜帶PC-3（前列腺）,HCT-116（結(jié)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(zhǎng)相關(guān)的SK-LMS-1異種移植模型中抑制mTOR信號(hào)傳導(dǎo). |
| 體內(nèi)活性 | Deforolimus劑量依賴(lài)性抑制HT-1080細(xì)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(dǎo)致細(xì)胞尺寸減小,G1期細(xì)胞增多,抑制葡萄糖攝取,EC50為0.1-1 nM。Deforolimus作用于一組細(xì)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(lài)性抑制VEGF產(chǎn)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(xì)胞系,具有協(xié)同作用,這種作用存在劑量依賴(lài)性,這種作用與細(xì)胞增殖受抑制而非細(xì)胞凋亡增多相關(guān),處理24小時(shí)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(xì)胞系（除了H157細(xì)胞）細(xì)胞生長(zhǎng),IC30為2.45-8.83 nM,而作用于H157細(xì)胞時(shí),IC30 >20 nM。2.8-5.9 nM Deforolimus處理A549,H1703和H157細(xì)胞（除了表達(dá)mTORC1耐藥變異的H1666）,使p70S6KThr389去磷酸化,提高A549和H1703細(xì)胞中pAKTser473和pAKTThr308磷酸化水平。 |
| 存儲(chǔ)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(guān)鍵字 | inhibit | Autophagy | MK 8669 | Mammalian target of Rapamycin | mTOR | Ridaforolimus | Inhibitor | MK8669 | AP-23573 | AP 23573 |
| 相關(guān)產(chǎn)品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Xylitol | Hydroxychloroquine | Curcumin | Stavudine | Myricetin | Paeonol | Sodium 4-phenylbutyrate |