Everolimus (RAD001) 化学構造
分子量: 958.22

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製品説明

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    mTOR製品生物活性の比較
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製品の説明

生物活性

製品説明 Everolimus (RAD001)は一種のmTOR阻害剤で、FKBP12に作用します。無細胞試験でIC50値は1.6-2.4 nMになります。
ターゲット mTOR (FKBP12)
IC50 1.6-2.4 nM [1]
In vitro試験 Everolimus exhibits the immunosuppressive activity which is comparable to that of rapamycin. Everolimus competes with immobilized FK 506 for binding to biotinylated FKBP12 and shows the inhibitory effect on a two-way MLR performed with spleen cells from BALB/c and CBA mice with IC50 of 0.12-1.8 nM. [1] Everolimus also shows antiangiogenic/vascular effects in VEGF-induced HUVEC proliferation with IC50 of 0.12 nM and bFGF-induced HUVEC proliferation with IC50 of 0.8 nM, respectively. [2] A recent study shows that Everolimus shows a dose-dependent inhibitory effects on both the total cells and the stem cells from the BT474 cell line and the primary breast cancer cells with IC50 of 156 nM in total cells of primary breast cancer cells and 71 nM in total cells of BT474 cells. In addition, combination treatment with Everolimus and trastuzumab produces the significantly increased inhibition on the growth of cancer stem cells with the inhibition rate increased by more than 50 %. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
SQ20B M1vOPGN6fG:2b4jpZ{BCe3OjeR?= MmPiO|IhcA>? MkfrSG1UVw>? NGG5WWxKSzVyPUWuOUDPxE1? NUi1c2w3OjR2NEWzNVE>
Colo205 NWD2fVVES3m2b4TvfIlkKEG|c3H5 NUPTZY9OPzJiaB?= M125WGROW09? MVnJR|UxRTJyIN88US=> NYrsN4E4OjR2NEWzNVE>
ColoR NGPOZ4JEgXSxdH;4bYMhSXO|YYm= NIDvRnc4OiCq NEj4[JJFVVOR NXuyPHc5UUN3ME24Mlch|ryP NUPyPVdNOjR2NEWzNVE>
HCT116 NV\hdoVKS3m2b4TvfIlkKEG|c3H5 NHnCfWI4OiCq NYfHb|VHTE2VTx?= MkjMTWM2OD1zMjFOwG0> MkXMNlQ1PDV|MUG=
HT29 Mlr2R5l1d3SxeHnjJGF{e2G7 MnPCO|IhcA>? NI\YdoNFVVOR NEOwXXhKSzVyPUG1JO69VQ>? MXmyOFQ1PTNzMR?=
CAKI1 NYjVS4pYS3m2b4TvfIlkKEG|c3H5 NF;yfGQ4OiCq NFvWVHpFVVOR MVrJR|UxRTF2IN88US=> MWKyOFQ1PTNzMR?=
SK-HEP1 MXzDfZRwfG:6aXOgRZN{[Xl? M4e4NlczKGh? MVHEUXNQ M2fRWWlEPTB;MUKg{txO MnHvNlQ1PDV|MUG=
DU145 M2i2dmN6fG:2b4jpZ{BCe3OjeR?= MkLtO|IhcA>? NVnScJRYTE2VTx?= MkHUTWM2OD16IN88US=> MnfwNlQ1PDV|MUG=
OVCAR3 NFTZN4dEgXSxdH;4bYMhSXO|YYm= MoHKO|IhcA>? MWDEUXNQ NXrQU2JTUUN3ME2xOkDPxE1? NX;GU4gyOjR2NEWzNVE>
HOP62 MlPOR5l1d3SxeHnjJGF{e2G7 NH;wcIE4OiCq MYjEUXNQ M4rRdWlEPTB;MUmg{txO NUjMXlllOjR2NEWzNVE>
Colo205 MXrGeY5kfGmxbjDBd5NigQ>? MneyNlQhcA>? MmHqSG1UVw>? MUHJcohq[mm2czDtWG9TSzFiaX6gbJVu[W5iQ1;MU|IxPSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gV|YheGixc4Doc5J6dGG2aX;uJIF1KDBwMTD0c{A5KHWP NUn6UXpDOjR6M{[wO|A>
Colo205 MWLGeY5kfGmxbjDBd5NigQ>? Ml;RNlQhcA>? M{LZNmROW09? M3u4eGlvcGmkaYTzJI1VV1KFMTDpckBpfW2jbjDDU2xQOjB3IHPlcIx{KGG|c3Xzd4VlKGG|IILl[JVkfGmxbjDv[kA1NUWEUEGgdIhwe3Cqb4L5cIF1cW:wIHH0JFAvOSC2bzC4JJVO MnS0NlQ5OzZyN{C=
SK-HEP1 MXPGeY5kfGmxbjDBd5NigQ>? MWmyOEBp MXTEUXNQ NWjlWYNxUW6qaXLpeJMhdVSRUlOxJIlvKGi3bXHuJHNMNUiHUEGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKFN4IIDoc5NxcG:{eXzheIlwdiCjdDCwMlEhfG9iODD1US=> MXqyOFg{PjB5MB?=
SK-HEP1 M4DoR2Z2dmO2aX;uJGF{e2G7 NFHi[mczPCCq NHLGOmVFVVOR MWjJcohq[mm2czDtWG9TSzFiaX6gbJVu[W5iU1utTGVROSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gOE1GSlBzIIDoc5NxcG:{eXzheIlwdiCjdDCwMlEhfG9iODD1US=> NIrnXVEzPDh|NkC3NC=>

... Click to View More Cell Line Experimental Data

In vivo試験 Everolimus (0.1 to 10 mg/kg) dose-dependently inhibits growth of the primary (ear) and lymph node metastases of B16/BL6 melanoma, with decreased total number of vessels and reduced mature vessels. [2] In a xenograft animal model of BT474 stem cells, Everolimus shows significant reductions in mean tumor sizes (590.6 mm3), compared to the control group with a tumor size of 698 mm3. Furthermore, combination treatment with Everolimus and trastuzumab significantly decreases the xenograft tumor size (410.8 mm3) more than Everolimus treatment alone. [3]
臨床試験 Everolimus is currently in Phase I clinical trials in patients with Unspecified Adult Solid Tumor.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

FKBP12 binding assay & Mixed lymphocyte reaction (MLR) FKBP12 binding assay: Binding to the FK 506 binding protein (FKBP12) is indirectly assessed by means of an ELISA-type competition assay. FK 506 is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to FK 506 (rIC50 = IC50 Everolimus/IC50 FK 506). Mixed lymphocyte reaction (MLR): The immunosuppressive activities of RAP and its derivatives are assessed in a two-way MLR, using spleen cells of BALB/c and CBA mice. RAP is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to RAP (rIC50 = IC50 Everolimus/IC50 RAP).

細胞アッセイ: [3]

細胞株 BT474 cell line and the primary breast cancer cells
濃度 0.001-10 μM
反応時間 24 hours
実験の流れ The 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction assay (MTT assay) is used to compare the effects of Everolimus or trastuzumab on total breast cancer cells and breast CSCs. The total cells and the stem cells from the BT474 cell line and the primary breast cancer cells are respectively seeded into 96-well plates with different concentrations of the drugs, with five wells for each concentration, and the cells are cultured at 37 °C with 5 % CO2 in an incubator for 24 hours. The concentrations of Everolimus are 1 nM, 10 nM, 100 nM, 1 μM and 10 μM, and the concentrations of trastuzumab are 0.5 μg/mL, 1 μg/mL, 10 μg/mL, 50 μg/mL, and 100 μg/mL. The combinatorial inhibitory effect of Everolimus and Trastuzumab on the in vitro growth of breast CSCs is examined by MTT assay as well using 10 μg/mL trastuzumab in combination of increasing concentrations of everolimus (1 nM, 10 nM, 100 nM and 1 μM). After drug treatment for 24 hours, 20 μL MTT [5 mg/mL in phosphate buffered saline (PBS)] is added to each well, and the cells are incubated at 37 °C with 5 % CO2 and saturated humidity for 4 hours. Following the subsequent removal of the supernatant, 150 μL dimethyl sulfoxide (DMSO) is added to each well, and the cells are vortexed for 10 minutes. The light absorbance (OD value) is measured for each well using an ELISA reader. Each experiment is repeated in triplicate, and dose–response curves are plotted. The probit software of the statistical software package SPSS 17.0 for Windows is used to calculate the inhibitory concentration (IC50) of Everolimus.

動物実験: [3]

動物モデル Cultured BT474 stem cells are injected beneath the left breast pad of BALB/c nude mice.
製剤 Everolimus is dissolved in saline.
投薬量 ≤2 mg/kg
投与方法 Administered via p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Everolimus (RAD001) SDF
分子量 958.22
化学式

C53H83NO14

CAS No. 159351-69-6
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 100 mg/mL (104.36 mM)
Ethanol 7 mg/mL (7.3 mM)
Water <1 mg/mL
In vivo 30% Propylene glycol (dissolve first)+5% Tween 80+ddH2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, rapamycin deriv

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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