Everolimus

製品コードS1120 バッチS112025

化学情報

	Synonyms	RAD001,SDZ-RAD	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₅₃H₈₃NO₁₄
	分子量	958.22	CAS No.	159351-69-6
Solubility (25°C)*	体外	DMSO	100 mg/mL (104.36 mM)
		Ethanol	100 mg/mL (104.36 mM)
		Water	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	エベロリムス (Everolimus (RAD001, SDZ-RAD)) は FKBP12 に結合することで形成した複合体により mTOR を阻害します。Cell-free assay における IC50 は1.6 ～ 2.4 ｎM です。エベロリムスはアポトーシス (apoptosis) とオートファジー (autophagy) を誘発することによりがん細胞の増殖を阻害します。
in vitro	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]
in vivo	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]

プロトコル(参考用のみ)

キナーゼアッセイ	FKBP12 binding assay & Mixed lymphocyte reaction (MLR)
キナーゼアッセイ	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	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	動物モデル	Cultured BT474 stem cells are injected beneath the left breast pad of BALB/c nude mice.
	投薬量	≤2 mg/kg
	投与方法	Administered via p.o.

参考

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カスタマーフィードバック

: Data from [Data independently produced by Br J Cancer, 2014, 111(6), 1168-79]

: Data from [Data independently produced by Clin Cancer Res, 2013, 19(3),598-609]

: Data from [Data independently produced by Cancer Cell, 2012, 21(2), 155-67]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Human fetal brain self-organizes into long-term expanding organoids [ Cell, 2024, 187(3):712-732.e38]	PubMed: 38194967
Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response [ Mol Ther Nucleic Acids, 2024, 35(1):102090]	PubMed: 38187140
NF1 deficiency drives metabolic reprogramming in ER+ breast cancer [ Mol Metab, 2024, 80:101876]	PubMed: 38216123
Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness [ Cancer Cell, 2023, 41(1):139-163.e17]	PubMed: 36563681
Metabolic support by macrophages sustains colonic epithelial homeostasis [ Cell Metab, 2023, S1550-4131(23)00341-8]	PubMed: 37804836
Cellular mechanisms of heterogeneity in NF2-mutant schwannoma [ Nat Commun, 2023, 14(1):1559]	PubMed: 36944680
N-acetylcysteine overcomes NF1 loss-driven resistance to PI3Kα inhibition in breast cancer [ Cell Rep Med, 2023, 4(4):101002]	PubMed: 37044095
HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101285]	PubMed: 37951219
Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth [ J Exp Clin Cancer Res, 2023, 42(1):25]	PubMed: 36670508
ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma [ Cancer Res, 2023, 83(12):2034-2051]	PubMed: 37078777

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人間や獣医の診断であるか治療的な使用のためにでない。

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